ChemWiki - User contributions [en]

It:Saxitoxin

2006-12-07T14:58:49Z

Ak705: /* References */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as [http://en.wikipedia.org/wiki/Paralytic_shellfish_poisoning paralytic shellfish poisoning] (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-

oxa-bicyclo[11.3.0]hexadeca-3t,11t-dien-

5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.

Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and

if swallowed.Very Toxic by inhalation

and if swallowed
|-
| Safety
| Wear suitable protective clothing and

eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.
[[Image:Saxsyn1.gif|Synthesis]]

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
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HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
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Saxitoxin has obvious dangers to public health via the contamination of foodstocks. But saxitoxin may also be used in chemical warfare. Saxitoxin is around 1000 times more toxic than a typical synthetic nerve gas such as sarin, and in the 1950s, the CIA began experimenting with it, reportedly using it in suicide capsules provided to its agents. In 1970, it is reported that President Nixon ordered the CIA to destroy its entire stock of saxitoxin as part of the US commitment in accordance with the United Nations agreement on biological weapons. Saxitoxin, along with a similar chemical called [http://en.wikipedia.org/wiki/Ricin ricin], currently appear on Schedule 1 of the [http://en.wikipedia.org/wiki/Chemical_Weapons_Convention Chemical Weapons Convention] (CWC) and are the only substances on this schedule to have some industrial use (besides nitrogen mustards), as these toxins are generally isolated from natural sources as opposed to the synthesis. The use of these two toxins is exhaustively monitored nationally and the CWC shall ensure that the toxins are adequately reported for arms control purposes, due to their harmful nature. However, in 1975 William Colby, Director of the CIA , revealed to Congress that they still possessed over 10 grammes of saxitoxin in Washington, and this supply was then distributed to scientists and medical researchers to prevent further use in chemical warfare. Saxitoxin has thus been used for the labelling, characterisation and isolation of various sodium channel components (due to its otherwise toxic effects on these) and this has opened up new avenues for the study of various nervous disorders.

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking [http://en.wikipedia.org/wiki/Sodium_channel sodium channels] in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

Saxitoxin is also used in nervous system experiments and has been used in mixtures to improve the function of several anaesthetics.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
*1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm
*2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html
*3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm
*4. https://www.iscid.org/encyclopedia/Saxitoxin
*5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html
*6. https://www.sigmaaldrich.com

It:Tamoxifen

2006-12-07T14:54:54Z

Ak705: /* What is Tamoxifen Used For? */

=Tamoxifen=
==Structures and 3D Image==
[[Image:Tamoxifen.png|left|10|Structure of Tamoxifen]]
Structure of Tamoxifen 1,2
<jmol>
<jmolApplet>
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<inlineContents>
HEADER CSD ENTRY TTAMOX01
COMPND UNNAMED
AUTHOR GENERATED BY CONQUEST
CRYST1 41.630 5.747 30.679 90.00 142.90 90.00 C 2/c 8
ATOM 1 C1 UNK 0 1 16.197 1.751 16.833 1.00 0.00
ATOM 2 C2 UNK 0 1 16.883 0.621 16.433 1.00 0.00
ATOM 3 C3 UNK 0 1 17.319 0.512 15.121 1.00 0.00
ATOM 4 C4 UNK 0 1 17.077 1.518 14.187 1.00 0.00
ATOM 5 C5 UNK 0 1 16.413 2.654 14.620 1.00 0.00
ATOM 6 C6 UNK 0 1 15.975 2.779 15.939 1.00 0.00
ATOM 7 C7 UNK 0 1 17.558 1.390 12.775 1.00 0.00
ATOM 8 C8 UNK 0 1 16.794 1.665 11.699 1.00 0.00
ATOM 9 C9 UNK 0 1 17.353 1.702 10.291 1.00 0.00
ATOM 10 C10 UNK 0 1 16.798 0.602 9.401 1.00 0.00
ATOM 11 O1 UNK 0 1 15.777 1.765 18.145 1.00 0.00
ATOM 12 C11 UNK 0 1 15.059 2.927 18.600 1.00 0.00
ATOM 13 C12 UNK 0 1 14.568 2.659 20.001 1.00 0.00
ATOM 14 C13 UNK 0 1 19.000 0.984 12.660 1.00 0.00
ATOM 15 C14 UNK 0 1 19.386 -0.194 12.044 1.00 0.00
ATOM 16 C15 UNK 0 1 20.751 -0.532 11.962 1.00 0.00
ATOM 17 C16 UNK 0 1 21.691 0.304 12.504 1.00 0.00
ATOM 18 C17 UNK 0 1 21.325 1.452 13.124 1.00 0.00
ATOM 19 C18 UNK 0 1 19.975 1.802 13.217 1.00 0.00
ATOM 20 C19 UNK 0 1 15.333 1.949 11.812 1.00 0.00
ATOM 21 C20 UNK 0 1 14.487 1.049 12.430 1.00 0.00
ATOM 22 C21 UNK 0 1 13.121 1.303 12.519 1.00 0.00
ATOM 23 C22 UNK 0 1 12.602 2.459 11.992 1.00 0.00
ATOM 24 C23 UNK 0 1 13.423 3.351 11.368 1.00 0.00
ATOM 25 C24 UNK 0 1 14.781 3.099 11.270 1.00 0.00
ATOM 26 C25 UNK 0 1 12.198 2.430 19.709 1.00 0.00
ATOM 27 N1 UNK 0 1 13.355 1.779 19.870 1.00 0.00
ATOM 28 C26 UNK 0 1 13.516 0.549 20.070 1.00 0.00
CONECT 1 2 6 11
CONECT 2 1 3
CONECT 3 2 4
CONECT 4 3 5 7
CONECT 5 4 6
CONECT 6 1 5
CONECT 7 4 8 14
CONECT 8 7 9 20
CONECT 9 8 10
CONECT 10 9
CONECT 11 1 12
CONECT 12 11 13
CONECT 13 12 27
CONECT 14 7 15 19
CONECT 15 14 16
CONECT 16 15 17
CONECT 17 16 18
CONECT 18 17 19
CONECT 19 14 18
CONECT 20 8 21 25
CONECT 21 20 22
CONECT 22 21 23
CONECT 23 22 24
CONECT 24 23 25
CONECT 25 20 24
CONECT 26 27
CONECT 27 13 26 28
CONECT 28 27
MASTER 0 0 0 0 0 0 0 0 28 0 28 0
END
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==Chemical Information==
{| border="1"
|-
! IUPAC name
|(Z) 2-[4-(1,2-diphenylbut-1-enyl)phenoxy]-N,N-dimethyl-ethanamine.
|-
! Chemical Formula
|C26H29NO
|-
!Molecular Weight
|371.52 g mol-1
|-
!Melting Point
|96-98oC
|-
! Type of Substance
|White, Odourless Crystals
|}
==What is Tamoxifen Used For?==
Tamoxifen is currently the most popular drug used for the treatment of breast cancer in women. Tamoxifen was discovered by AstraZeneca (formally known as ICI Pharmaceuticals) and is commercially known as Nolvadex, Istubal and Valodex. It is taken as a tablet

It has also been found that Tamoxifen can be used to treat other ailments, such as osteoporosis and gynecomastia in men.

Tamoxifen is occasionally used to improve the rare condition known as [http://en.wikipedia.org/wiki/Retroperitoneal_fibrosis retroperitoneal fibrosis] (or Ormond's disease), although the exact mechanism of this reaction is still unknown. This condition involves an excess of [http://en.wikipedia.org/wiki/Fibrous_tissue fibrous tissue] and scar tissue in the part of the body which contains the [http://en.wikipedia.org/wiki/Kidney kidneys], [http://en.wikipedia.org/wiki/Aorta aorta], [http://en.wikipedia.org/wiki/Urinary_system renal tract] and various other structures. Symptoms of the condition improved within weeks, and within months signs of inflammation decreased and the scar tissue shrunk.

==How Does Tamoxifen Work?==
The primary function of Tamoxifen is as an anti-oestrogen drug, which means it reduces or stops the action of oestrogen.[http://www.cancer-info.com/tamoxifen.htm 3]

Breast cancer is hormone-related and relies on the supply of sex hormones, particularly oestrogen, to grow. Cancers with oestrogen receptors on the surface of their cells are called `oestrogen receptor positive' (ER positive). Oestrogen can fit directly into the active site on these receptors and causes the cells to divide and the tumour to grow (see Figure 1).[http://www.fareston.com/d_living/d3.html 4]

Tamoxifen has a similar structure to oestrogen and works by imitating the action of oestrogen and fits into the active sites of the receptors. However, tamoxifen does not cause the cells to divide, but remains in place and prevents the oestrogen from getting to the cancer cells, therefore they either grow more slowly or stop growing altogether (see Figure 2).
[[Image:Figure_1.jpg|200|Action of oestrogen binding to oestrogen receptor]] [[Image:Figure_2.jpg|200|Action of Tamoxifen blocking oestrogen binding to cancer cell]]

==How is Tamoxifen made?==
===Synthesis of Tamoxifen via a carbometalation of alkynylsilanes===
====Step 1====
[[Image:step1tamoxifen.PNG|200|1st step in reaction path for tamoxifen]]
This is the 1st step in this synthesis. The reagents are Et2AlCl, Cp2TiCl2, CH2Cl2. The product of this step in the reaction is then cleaved with NBS (N-bromosuccinimide)at -78oC or 195.15K. The yield for this step is shown below the arrow.
====Step 2====
[[Image:step2tamoxifen.PNG|200|2nd step in reaction path for tamoxifen]]
This is the next step in the synthesis of tamoxifen. The reagents are PhZnCl, Pd(PPh3)4 (this is the catalyst), THF, and this is under reflux.
====Step 3====
[[Image:step3tamoxifen.PNG|200|3rd step in reaction path for tamoxifen]]
The reagents for the step are Br2, CH2Cl, NaOMe/MeOH, Temperature is -78oC to Room Temperature
====Step 4====
[[Image:step4tamoxifen.PNG|200|4th step in reaction path for tamoxifen]]
The reagents are p-MeOC , H4ZnCl, Pd(PPh3)4 (this is the catalyst), THF. The reaction happens under reflux.
====Step 5====
[[Image:step5tamoxifen.PNG|200|last step in reaction path for tamoxifen]]
This last step takes place in 4 smaller steps. The 1 of these steps has the reagents NaSEt, DMF, and takes place under reflux. 2nd has reagents ClCH3, CH2NMe2, HCl, NaOEt, EtOH and also takes place under reflux conditions. 3rd: HCl(g) Et2O. The last step has reagent 0.5M NaOH 6

==Side Effects of using Tamoxifen==
The most common side-effects of taking Tamoxifen in pre-menopausal women are:
*nausea
*hot flushes and sweats
some less common side-effects include
*headaches
*tiredness
*dizziness.

For post-menopausal women who take Tamoxifen over a long period of time, there is a slightly increased risk of developing endometrial cancer, however, if detected early, treatment for this is usually successful and the benefits of taking Tamoxifen in treating breast-cancer far outweigh this small risk.[http://www.cancerbackup.org.uk/Treatments/Hormonaltherapies/Individualhormonaltherapies/Tamoxifen 5]

==References==
*1 - MDS Crossfire Commander Beilstein: Structure
*2 - Conquest (Cambridge Crystal Structure Database): 3D image
*3 - www.cancer-info.com/tamoxifen.htm
*4 - www.fareston.com/d_living/d3.html
*5 - www.cancerbackup.org.uk/Treatments/Hormonaltherapies/Individualhormonaltherapies/Tamoxifen
*6 - R. Bryan Miller, Mohammed I. Al-Hassan ''Stereospecific Synthesis of (Z) - Tamoxifen via Carbometalation of Alkynylsilanes'' J. Org. Chem. 1985 '''50''', 2121-2123
*7 - http://www.annals.org/cgi/content/full/144/2/I-51
*8 - http://en.wikipedia.org/wiki/Retroperitoneal_fibrosis

It:Tamoxifen

2006-12-07T14:52:02Z

Ak705: /* References */

=Tamoxifen=
==Structures and 3D Image==
[[Image:Tamoxifen.png|left|10|Structure of Tamoxifen]]
Structure of Tamoxifen 1,2
<jmol>
<jmolApplet>
<size>400</size>
<color>white</color>
<script>zoom 150; ball and stick on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER CSD ENTRY TTAMOX01
COMPND UNNAMED
AUTHOR GENERATED BY CONQUEST
CRYST1 41.630 5.747 30.679 90.00 142.90 90.00 C 2/c 8
ATOM 1 C1 UNK 0 1 16.197 1.751 16.833 1.00 0.00
ATOM 2 C2 UNK 0 1 16.883 0.621 16.433 1.00 0.00
ATOM 3 C3 UNK 0 1 17.319 0.512 15.121 1.00 0.00
ATOM 4 C4 UNK 0 1 17.077 1.518 14.187 1.00 0.00
ATOM 5 C5 UNK 0 1 16.413 2.654 14.620 1.00 0.00
ATOM 6 C6 UNK 0 1 15.975 2.779 15.939 1.00 0.00
ATOM 7 C7 UNK 0 1 17.558 1.390 12.775 1.00 0.00
ATOM 8 C8 UNK 0 1 16.794 1.665 11.699 1.00 0.00
ATOM 9 C9 UNK 0 1 17.353 1.702 10.291 1.00 0.00
ATOM 10 C10 UNK 0 1 16.798 0.602 9.401 1.00 0.00
ATOM 11 O1 UNK 0 1 15.777 1.765 18.145 1.00 0.00
ATOM 12 C11 UNK 0 1 15.059 2.927 18.600 1.00 0.00
ATOM 13 C12 UNK 0 1 14.568 2.659 20.001 1.00 0.00
ATOM 14 C13 UNK 0 1 19.000 0.984 12.660 1.00 0.00
ATOM 15 C14 UNK 0 1 19.386 -0.194 12.044 1.00 0.00
ATOM 16 C15 UNK 0 1 20.751 -0.532 11.962 1.00 0.00
ATOM 17 C16 UNK 0 1 21.691 0.304 12.504 1.00 0.00
ATOM 18 C17 UNK 0 1 21.325 1.452 13.124 1.00 0.00
ATOM 19 C18 UNK 0 1 19.975 1.802 13.217 1.00 0.00
ATOM 20 C19 UNK 0 1 15.333 1.949 11.812 1.00 0.00
ATOM 21 C20 UNK 0 1 14.487 1.049 12.430 1.00 0.00
ATOM 22 C21 UNK 0 1 13.121 1.303 12.519 1.00 0.00
ATOM 23 C22 UNK 0 1 12.602 2.459 11.992 1.00 0.00
ATOM 24 C23 UNK 0 1 13.423 3.351 11.368 1.00 0.00
ATOM 25 C24 UNK 0 1 14.781 3.099 11.270 1.00 0.00
ATOM 26 C25 UNK 0 1 12.198 2.430 19.709 1.00 0.00
ATOM 27 N1 UNK 0 1 13.355 1.779 19.870 1.00 0.00
ATOM 28 C26 UNK 0 1 13.516 0.549 20.070 1.00 0.00
CONECT 1 2 6 11
CONECT 2 1 3
CONECT 3 2 4
CONECT 4 3 5 7
CONECT 5 4 6
CONECT 6 1 5
CONECT 7 4 8 14
CONECT 8 7 9 20
CONECT 9 8 10
CONECT 10 9
CONECT 11 1 12
CONECT 12 11 13
CONECT 13 12 27
CONECT 14 7 15 19
CONECT 15 14 16
CONECT 16 15 17
CONECT 17 16 18
CONECT 18 17 19
CONECT 19 14 18
CONECT 20 8 21 25
CONECT 21 20 22
CONECT 22 21 23
CONECT 23 22 24
CONECT 24 23 25
CONECT 25 20 24
CONECT 26 27
CONECT 27 13 26 28
CONECT 28 27
MASTER 0 0 0 0 0 0 0 0 28 0 28 0
END
</inlineContents>
</jmolApplet>
</jmol>

==Chemical Information==
{| border="1"
|-
! IUPAC name
|(Z) 2-[4-(1,2-diphenylbut-1-enyl)phenoxy]-N,N-dimethyl-ethanamine.
|-
! Chemical Formula
|C26H29NO
|-
!Molecular Weight
|371.52 g mol-1
|-
!Melting Point
|96-98oC
|-
! Type of Substance
|White, Odourless Crystals
|}
==What is Tamoxifen Used For?==
Tamoxifen is currently the most popular drug used for the treatment of breast cancer in women. Tamoxifen was discovered by AstraZeneca (formally known as ICI Pharmaceuticals) and is commercially known as Nolvadex, Istubal and Valodex. It is taken as a tablet

It has also been found that Tamoxifen can be used to treat other ailments, such as osteoporosis and gynecomastia in men.

Tamoxifen is occasionally used to improve the rare condition known as retroperitoneal fibrosis (or Ormond's disease), although the exact mechanism of this reaction is still unknown. This condition involves an excess of fibrous tissue and scar tissue in the part of the body which contains the kidneys, aorta, renal tract and various other structures. Symptoms of the condition improved within weeks, and within months signs of inflammation decreased and the scar tissue shrunk.

==How Does Tamoxifen Work?==
The primary function of Tamoxifen is as an anti-oestrogen drug, which means it reduces or stops the action of oestrogen.[http://www.cancer-info.com/tamoxifen.htm 3]

Breast cancer is hormone-related and relies on the supply of sex hormones, particularly oestrogen, to grow. Cancers with oestrogen receptors on the surface of their cells are called `oestrogen receptor positive' (ER positive). Oestrogen can fit directly into the active site on these receptors and causes the cells to divide and the tumour to grow (see Figure 1).[http://www.fareston.com/d_living/d3.html 4]

Tamoxifen has a similar structure to oestrogen and works by imitating the action of oestrogen and fits into the active sites of the receptors. However, tamoxifen does not cause the cells to divide, but remains in place and prevents the oestrogen from getting to the cancer cells, therefore they either grow more slowly or stop growing altogether (see Figure 2).
[[Image:Figure_1.jpg|200|Action of oestrogen binding to oestrogen receptor]] [[Image:Figure_2.jpg|200|Action of Tamoxifen blocking oestrogen binding to cancer cell]]

==How is Tamoxifen made?==
===Synthesis of Tamoxifen via a carbometalation of alkynylsilanes===
====Step 1====
[[Image:step1tamoxifen.PNG|200|1st step in reaction path for tamoxifen]]
This is the 1st step in this synthesis. The reagents are Et2AlCl, Cp2TiCl2, CH2Cl2. The product of this step in the reaction is then cleaved with NBS (N-bromosuccinimide)at -78oC or 195.15K. The yield for this step is shown below the arrow.
====Step 2====
[[Image:step2tamoxifen.PNG|200|2nd step in reaction path for tamoxifen]]
This is the next step in the synthesis of tamoxifen. The reagents are PhZnCl, Pd(PPh3)4 (this is the catalyst), THF, and this is under reflux.
====Step 3====
[[Image:step3tamoxifen.PNG|200|3rd step in reaction path for tamoxifen]]
The reagents for the step are Br2, CH2Cl, NaOMe/MeOH, Temperature is -78oC to Room Temperature
====Step 4====
[[Image:step4tamoxifen.PNG|200|4th step in reaction path for tamoxifen]]
The reagents are p-MeOC , H4ZnCl, Pd(PPh3)4 (this is the catalyst), THF. The reaction happens under reflux.
====Step 5====
[[Image:step5tamoxifen.PNG|200|last step in reaction path for tamoxifen]]
This last step takes place in 4 smaller steps. The 1 of these steps has the reagents NaSEt, DMF, and takes place under reflux. 2nd has reagents ClCH3, CH2NMe2, HCl, NaOEt, EtOH and also takes place under reflux conditions. 3rd: HCl(g) Et2O. The last step has reagent 0.5M NaOH 6

==Side Effects of using Tamoxifen==
The most common side-effects of taking Tamoxifen in pre-menopausal women are:
*nausea
*hot flushes and sweats
some less common side-effects include
*headaches
*tiredness
*dizziness.

For post-menopausal women who take Tamoxifen over a long period of time, there is a slightly increased risk of developing endometrial cancer, however, if detected early, treatment for this is usually successful and the benefits of taking Tamoxifen in treating breast-cancer far outweigh this small risk.[http://www.cancerbackup.org.uk/Treatments/Hormonaltherapies/Individualhormonaltherapies/Tamoxifen 5]

==References==
*1 - MDS Crossfire Commander Beilstein: Structure
*2 - Conquest (Cambridge Crystal Structure Database): 3D image
*3 - www.cancer-info.com/tamoxifen.htm
*4 - www.fareston.com/d_living/d3.html
*5 - www.cancerbackup.org.uk/Treatments/Hormonaltherapies/Individualhormonaltherapies/Tamoxifen
*6 - R. Bryan Miller, Mohammed I. Al-Hassan ''Stereospecific Synthesis of (Z) - Tamoxifen via Carbometalation of Alkynylsilanes'' J. Org. Chem. 1985 '''50''', 2121-2123
*7 - http://www.annals.org/cgi/content/full/144/2/I-51
*8 - http://en.wikipedia.org/wiki/Retroperitoneal_fibrosis

It:Tamoxifen

2006-12-07T14:51:05Z

Ak705: /* What is Tamoxifen Used For? */

=Tamoxifen=
==Structures and 3D Image==
[[Image:Tamoxifen.png|left|10|Structure of Tamoxifen]]
Structure of Tamoxifen 1,2
<jmol>
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<size>400</size>
<color>white</color>
<script>zoom 150; ball and stick on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER CSD ENTRY TTAMOX01
COMPND UNNAMED
AUTHOR GENERATED BY CONQUEST
CRYST1 41.630 5.747 30.679 90.00 142.90 90.00 C 2/c 8
ATOM 1 C1 UNK 0 1 16.197 1.751 16.833 1.00 0.00
ATOM 2 C2 UNK 0 1 16.883 0.621 16.433 1.00 0.00
ATOM 3 C3 UNK 0 1 17.319 0.512 15.121 1.00 0.00
ATOM 4 C4 UNK 0 1 17.077 1.518 14.187 1.00 0.00
ATOM 5 C5 UNK 0 1 16.413 2.654 14.620 1.00 0.00
ATOM 6 C6 UNK 0 1 15.975 2.779 15.939 1.00 0.00
ATOM 7 C7 UNK 0 1 17.558 1.390 12.775 1.00 0.00
ATOM 8 C8 UNK 0 1 16.794 1.665 11.699 1.00 0.00
ATOM 9 C9 UNK 0 1 17.353 1.702 10.291 1.00 0.00
ATOM 10 C10 UNK 0 1 16.798 0.602 9.401 1.00 0.00
ATOM 11 O1 UNK 0 1 15.777 1.765 18.145 1.00 0.00
ATOM 12 C11 UNK 0 1 15.059 2.927 18.600 1.00 0.00
ATOM 13 C12 UNK 0 1 14.568 2.659 20.001 1.00 0.00
ATOM 14 C13 UNK 0 1 19.000 0.984 12.660 1.00 0.00
ATOM 15 C14 UNK 0 1 19.386 -0.194 12.044 1.00 0.00
ATOM 16 C15 UNK 0 1 20.751 -0.532 11.962 1.00 0.00
ATOM 17 C16 UNK 0 1 21.691 0.304 12.504 1.00 0.00
ATOM 18 C17 UNK 0 1 21.325 1.452 13.124 1.00 0.00
ATOM 19 C18 UNK 0 1 19.975 1.802 13.217 1.00 0.00
ATOM 20 C19 UNK 0 1 15.333 1.949 11.812 1.00 0.00
ATOM 21 C20 UNK 0 1 14.487 1.049 12.430 1.00 0.00
ATOM 22 C21 UNK 0 1 13.121 1.303 12.519 1.00 0.00
ATOM 23 C22 UNK 0 1 12.602 2.459 11.992 1.00 0.00
ATOM 24 C23 UNK 0 1 13.423 3.351 11.368 1.00 0.00
ATOM 25 C24 UNK 0 1 14.781 3.099 11.270 1.00 0.00
ATOM 26 C25 UNK 0 1 12.198 2.430 19.709 1.00 0.00
ATOM 27 N1 UNK 0 1 13.355 1.779 19.870 1.00 0.00
ATOM 28 C26 UNK 0 1 13.516 0.549 20.070 1.00 0.00
CONECT 1 2 6 11
CONECT 2 1 3
CONECT 3 2 4
CONECT 4 3 5 7
CONECT 5 4 6
CONECT 6 1 5
CONECT 7 4 8 14
CONECT 8 7 9 20
CONECT 9 8 10
CONECT 10 9
CONECT 11 1 12
CONECT 12 11 13
CONECT 13 12 27
CONECT 14 7 15 19
CONECT 15 14 16
CONECT 16 15 17
CONECT 17 16 18
CONECT 18 17 19
CONECT 19 14 18
CONECT 20 8 21 25
CONECT 21 20 22
CONECT 22 21 23
CONECT 23 22 24
CONECT 24 23 25
CONECT 25 20 24
CONECT 26 27
CONECT 27 13 26 28
CONECT 28 27
MASTER 0 0 0 0 0 0 0 0 28 0 28 0
END
</inlineContents>
</jmolApplet>
</jmol>

==Chemical Information==
{| border="1"
|-
! IUPAC name
|(Z) 2-[4-(1,2-diphenylbut-1-enyl)phenoxy]-N,N-dimethyl-ethanamine.
|-
! Chemical Formula
|C26H29NO
|-
!Molecular Weight
|371.52 g mol-1
|-
!Melting Point
|96-98oC
|-
! Type of Substance
|White, Odourless Crystals
|}
==What is Tamoxifen Used For?==
Tamoxifen is currently the most popular drug used for the treatment of breast cancer in women. Tamoxifen was discovered by AstraZeneca (formally known as ICI Pharmaceuticals) and is commercially known as Nolvadex, Istubal and Valodex. It is taken as a tablet

It has also been found that Tamoxifen can be used to treat other ailments, such as osteoporosis and gynecomastia in men.

Tamoxifen is occasionally used to improve the rare condition known as retroperitoneal fibrosis (or Ormond's disease), although the exact mechanism of this reaction is still unknown. This condition involves an excess of fibrous tissue and scar tissue in the part of the body which contains the kidneys, aorta, renal tract and various other structures. Symptoms of the condition improved within weeks, and within months signs of inflammation decreased and the scar tissue shrunk.

==How Does Tamoxifen Work?==
The primary function of Tamoxifen is as an anti-oestrogen drug, which means it reduces or stops the action of oestrogen.[http://www.cancer-info.com/tamoxifen.htm 3]

Breast cancer is hormone-related and relies on the supply of sex hormones, particularly oestrogen, to grow. Cancers with oestrogen receptors on the surface of their cells are called `oestrogen receptor positive' (ER positive). Oestrogen can fit directly into the active site on these receptors and causes the cells to divide and the tumour to grow (see Figure 1).[http://www.fareston.com/d_living/d3.html 4]

Tamoxifen has a similar structure to oestrogen and works by imitating the action of oestrogen and fits into the active sites of the receptors. However, tamoxifen does not cause the cells to divide, but remains in place and prevents the oestrogen from getting to the cancer cells, therefore they either grow more slowly or stop growing altogether (see Figure 2).
[[Image:Figure_1.jpg|200|Action of oestrogen binding to oestrogen receptor]] [[Image:Figure_2.jpg|200|Action of Tamoxifen blocking oestrogen binding to cancer cell]]

==How is Tamoxifen made?==
===Synthesis of Tamoxifen via a carbometalation of alkynylsilanes===
====Step 1====
[[Image:step1tamoxifen.PNG|200|1st step in reaction path for tamoxifen]]
This is the 1st step in this synthesis. The reagents are Et2AlCl, Cp2TiCl2, CH2Cl2. The product of this step in the reaction is then cleaved with NBS (N-bromosuccinimide)at -78oC or 195.15K. The yield for this step is shown below the arrow.
====Step 2====
[[Image:step2tamoxifen.PNG|200|2nd step in reaction path for tamoxifen]]
This is the next step in the synthesis of tamoxifen. The reagents are PhZnCl, Pd(PPh3)4 (this is the catalyst), THF, and this is under reflux.
====Step 3====
[[Image:step3tamoxifen.PNG|200|3rd step in reaction path for tamoxifen]]
The reagents for the step are Br2, CH2Cl, NaOMe/MeOH, Temperature is -78oC to Room Temperature
====Step 4====
[[Image:step4tamoxifen.PNG|200|4th step in reaction path for tamoxifen]]
The reagents are p-MeOC , H4ZnCl, Pd(PPh3)4 (this is the catalyst), THF. The reaction happens under reflux.
====Step 5====
[[Image:step5tamoxifen.PNG|200|last step in reaction path for tamoxifen]]
This last step takes place in 4 smaller steps. The 1 of these steps has the reagents NaSEt, DMF, and takes place under reflux. 2nd has reagents ClCH3, CH2NMe2, HCl, NaOEt, EtOH and also takes place under reflux conditions. 3rd: HCl(g) Et2O. The last step has reagent 0.5M NaOH 6

==Side Effects of using Tamoxifen==
The most common side-effects of taking Tamoxifen in pre-menopausal women are:
*nausea
*hot flushes and sweats
some less common side-effects include
*headaches
*tiredness
*dizziness.

For post-menopausal women who take Tamoxifen over a long period of time, there is a slightly increased risk of developing endometrial cancer, however, if detected early, treatment for this is usually successful and the benefits of taking Tamoxifen in treating breast-cancer far outweigh this small risk.[http://www.cancerbackup.org.uk/Treatments/Hormonaltherapies/Individualhormonaltherapies/Tamoxifen 5]

==References==
*1 - MDS Crossfire Commander Beilstein: Structure
*2 - Conquest (Cambridge Crystal Structure Database): 3D image
*3 - www.cancer-info.com/tamoxifen.htm
*4 - www.fareston.com/d_living/d3.html
*5 - www.cancerbackup.org.uk/Treatments/Hormonaltherapies/Individualhormonaltherapies/Tamoxifen
*6 - R. Bryan Miller, Mohammed I. Al-Hassan ''Stereospecific Synthesis of (Z) - Tamoxifen via Carbometalation of Alkynylsilanes'' J. Org. Chem. 1985 '''50''', 2121-2123

It:Saxitoxin

2006-12-07T14:38:52Z

Ak705: /* Saxitoxin: A Chemical Weapon */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as [http://en.wikipedia.org/wiki/Paralytic_shellfish_poisoning paralytic shellfish poisoning] (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-

oxa-bicyclo[11.3.0]hexadeca-3t,11t-dien-

5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.

Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and

if swallowed.Very Toxic by inhalation

and if swallowed
|-
| Safety
| Wear suitable protective clothing and

eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.
[[Image:Saxsyn1.gif|Synthesis]]

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
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<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
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Saxitoxin has obvious dangers to public health via the contamination of foodstocks. But saxitoxin may also be used in chemical warfare. Saxitoxin is around 1000 times more toxic than a typical synthetic nerve gas such as sarin, and in the 1950s, the CIA began experimenting with it, reportedly using it in suicide capsules provided to its agents. In 1970, it is reported that President Nixon ordered the CIA to destroy its entire stock of saxitoxin as part of the US commitment in accordance with the United Nations agreement on biological weapons. Saxitoxin, along with a similar chemical called [http://en.wikipedia.org/wiki/Ricin ricin], currently appear on Schedule 1 of the [http://en.wikipedia.org/wiki/Chemical_Weapons_Convention Chemical Weapons Convention] (CWC) and are the only substances on this schedule to have some industrial use (besides nitrogen mustards), as these toxins are generally isolated from natural sources as opposed to the synthesis. The use of these two toxins is exhaustively monitored nationally and the CWC shall ensure that the toxins are adequately reported for arms control purposes, due to their harmful nature. However, in 1975 William Colby, Director of the CIA , revealed to Congress that they still possessed over 10 grammes of saxitoxin in Washington, and this supply was then distributed to scientists and medical researchers to prevent further use in chemical warfare. Saxitoxin has thus been used for the labelling, characterisation and isolation of various sodium channel components (due to its otherwise toxic effects on these) and this has opened up new avenues for the study of various nervous disorders.

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking [http://en.wikipedia.org/wiki/Sodium_channel sodium channels] in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

Saxitoxin is also used in nervous system experiments and has been used in mixtures to improve the function of several anaesthetics.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T14:35:59Z

Ak705: /* Effects of Saxitoxin */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as [http://en.wikipedia.org/wiki/Paralytic_shellfish_poisoning paralytic shellfish poisoning] (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-

oxa-bicyclo[11.3.0]hexadeca-3t,11t-dien-

5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.

Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and

if swallowed.Very Toxic by inhalation

and if swallowed
|-
| Safety
| Wear suitable protective clothing and

eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.
[[Image:Saxsyn1.gif|Synthesis]]

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>

Saxitoxin has obvious dangers to public health via the contamination of foodstocks. But saxitoxin may also be used in chemical warfare. Saxitoxin is around 1000 times more toxic than a typical synthetic nerve gas such as sarin, and in the 1950s, the CIA began experimenting with it, reportedly using it in suicide capsules provided to its agents. In 1970, it is reported that President Nixon ordered the CIA to destroy its entire stock of saxitoxin as part of the US commitment in accordance with the United Nations agreement on biological weapons. Saxitoxin, along with a similar chemical called [http://en.wikipedia.org/wiki/Ricin ricin], currently appear on Schedule 1 of the Chemical Weapons Convention (CWC) and are the only substances on this schedule to have some industrial use (besides nitrogen mustards), as these toxins are generally isolated from natural sources as opposed to the synthesis. The use of these two toxins is exhaustively monitored nationally and the CWC shall ensure that the toxins are adequately reported for arms control purposes, due to their harmful nature. However, in 1975 William Colby, Director of the CIA , revealed to Congress that they still possessed over 10 grammes of saxitoxin in Washington, and this supply was then distributed to scientists and medical researchers to prevent further use in chemical warfare. Saxitoxin has thus been used for the labelling, characterisation and isolation of various sodium channel components (due to its otherwise toxic effects on these) and this has opened up new avenues for the study of various nervous disorders.

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking [http://en.wikipedia.org/wiki/Sodium_channel sodium channels] in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

Saxitoxin is also used in nervous system experiments and has been used in mixtures to improve the function of several anaesthetics.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T14:34:32Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as [http://en.wikipedia.org/wiki/Paralytic_shellfish_poisoning paralytic shellfish poisoning] (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-

oxa-bicyclo[11.3.0]hexadeca-3t,11t-dien-

5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.

Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and

if swallowed.Very Toxic by inhalation

and if swallowed
|-
| Safety
| Wear suitable protective clothing and

eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.
[[Image:Saxsyn1.gif|Synthesis]]

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>

Saxitoxin has obvious dangers to public health via the contamination of foodstocks. But saxitoxin may also be used in chemical warfare. Saxitoxin is around 1000 times more toxic than a typical synthetic nerve gas such as sarin, and in the 1950s, the CIA began experimenting with it, reportedly using it in suicide capsules provided to its agents. In 1970, it is reported that President Nixon ordered the CIA to destroy its entire stock of saxitoxin as part of the US commitment in accordance with the United Nations agreement on biological weapons. Saxitoxin, along with a similar chemical called [http://en.wikipedia.org/wiki/Ricin ricin], currently appear on Schedule 1 of the Chemical Weapons Convention (CWC) and are the only substances on this schedule to have some industrial use (besides nitrogen mustards), as these toxins are generally isolated from natural sources as opposed to the synthesis. The use of these two toxins is exhaustively monitored nationally and the CWC shall ensure that the toxins are adequately reported for arms control purposes, due to their harmful nature. However, in 1975 William Colby, Director of the CIA , revealed to Congress that they still possessed over 10 grammes of saxitoxin in Washington, and this supply was then distributed to scientists and medical researchers to prevent further use in chemical warfare. Saxitoxin has thus been used for the labelling, characterisation and isolation of various sodium channel components (due to its otherwise toxic effects on these) and this has opened up new avenues for the study of various nervous disorders.

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

Saxitoxin is also used in nervous system experiments and has been used in mixtures to improve the function of several anaesthetics.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T14:31:22Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-

oxa-bicyclo[11.3.0]hexadeca-3t,11t-dien-

5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.

Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and

if swallowed.Very Toxic by inhalation

and if swallowed
|-
| Safety
| Wear suitable protective clothing and

eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.
[[Image:Saxsyn1.gif|Synthesis]]

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>

Saxitoxin has obvious dangers to public health via the contamination of foodstocks. But saxitoxin may also be used in chemical warfare. Saxitoxin is around 1000 times more toxic than a typical synthetic nerve gas such as sarin, and in the 1950s, the CIA began experimenting with it, reportedly using it in suicide capsules provided to its agents. In 1970, it is reported that President Nixon ordered the CIA to destroy its entire stock of saxitoxin as part of the US commitment in accordance with the United Nations agreement on biological weapons. Saxitoxin, along with a similar chemical called [http://en.wikipedia.org/wiki/Ricin ricin], currently appear on Schedule 1 of the Chemical Weapons Convention (CWC) and are the only substances on this schedule to have some industrial use (besides nitrogen mustards), as these toxins are generally isolated from natural sources as opposed to the synthesis. The use of these two toxins is exhaustively monitored nationally and the CWC shall ensure that the toxins are adequately reported for arms control purposes, due to their harmful nature. However, in 1975 William Colby, Director of the CIA , revealed to Congress that they still possessed over 10 grammes of saxitoxin in Washington, and this supply was then distributed to scientists and medical researchers to prevent further use in chemical warfare. Saxitoxin has thus been used for the labelling, characterisation and isolation of various sodium channel components (due to its otherwise toxic effects on these) and this has opened up new avenues for the study of various nervous disorders.

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

Saxitoxin is also used in nervous system experiments and has been used in mixtures to improve the function of several anaesthetics.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T14:28:02Z

Ak705: /* Effects of Saxitoxin */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-

oxa-bicyclo[11.3.0]hexadeca-3t,11t-dien-

5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.

Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and

if swallowed.Very Toxic by inhalation

and if swallowed
|-
| Safety
| Wear suitable protective clothing and

eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.
[[Image:Saxsyn1.gif|Synthesis]]

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>

Saxitoxin has obvious dangers to public health via the contamination of foodstocks. But saxitoxin may also be used in chemical warfare. Saxitoxin is around 1000 times more toxic than a typical synthetic nerve gas such as sarin, and in the 1950s, the CIA began experimenting with it, reportedly using it in suicide capsules provided to its agents. In 1970, it is reported that President Nixon ordered the CIA to destroy its entire stock of saxitoxin as part of the US commitment in accordance with the United Nations agreement on biological weapons. Saxitoxin, along with a similar chemical called ricin, currently appear on Schedule 1 of the Chemical Weapons Convention (CWC) and are the only substances on this schedule to have some industrial use (besides nitrogen mustards), as these toxins are generally isolated from natural sources as opposed to the synthesis. The use of these two toxins is exhaustively monitored nationally and the CWC shall ensure that the toxins are adequately reported for arms control purposes, due to their harmful nature. However, in 1975 William Colby, Director of the CIA , revealed to Congress that they still possessed over 10 grammes of saxitoxin in Washington, and this supply was then distributed to scientists and medical researchers to prevent further use in chemical warfare. Saxitoxin has thus been used for the labelling, characterisation and isolation of various sodium channel components (due to its otherwise toxic effects on these) and this has opened up new avenues for the study of various nervous disorders.

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

Saxitoxin is also used in nervous system experiments and has been used in mixtures to improve the function of several anaesthetics.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T14:25:06Z

Ak705: /* Saxitoxin: A Chemical Weapon */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-

oxa-bicyclo[11.3.0]hexadeca-3t,11t-dien-

5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.

Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and

if swallowed.Very Toxic by inhalation

and if swallowed
|-
| Safety
| Wear suitable protective clothing and

eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.
[[Image:Saxsyn1.gif|Synthesis]]

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>

Saxitoxin has obvious dangers to public health via the contamination of foodstocks. But saxitoxin may also be used in chemical warfare. Saxitoxin is around 1000 times more toxic than a typical synthetic nerve gas such as sarin, and in the 1950s, the CIA began experimenting with it, reportedly using it in suicide capsules provided to its agents. In 1970, it is reported that President Nixon ordered the CIA to destroy its entire stock of saxitoxin as part of the US commitment in accordance with the United Nations agreement on biological weapons. Saxitoxin, along with a similar chemical called ricin, currently appear on Schedule 1 of the Chemical Weapons Convention (CWC) and are the only substances on this schedule to have some industrial use (besides nitrogen mustards), as these toxins are generally isolated from natural sources as opposed to the synthesis. The use of these two toxins is exhaustively monitored nationally and the CWC shall ensure that the toxins are adequately reported for arms control purposes, due to their harmful nature. However, in 1975 William Colby, Director of the CIA , revealed to Congress that they still possessed over 10 grammes of saxitoxin in Washington, and this supply was then distributed to scientists and medical researchers to prevent further use in chemical warfare. Saxitoxin has thus been used for the labelling, characterisation and isolation of various sodium channel components (due to its otherwise toxic effects on these) and this has opened up new avenues for the study of various nervous disorders.

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T14:09:34Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-

oxa-bicyclo[11.3.0]hexadeca-3t,11t-dien-

5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.

Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and

if swallowed.Very Toxic by inhalation

and if swallowed
|-
| Safety
| Wear suitable protective clothing and

eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.
[[Image:Saxsyn1.gif|Synthesis]]

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T14:09:11Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-

oxa-bicyclo[11.3.0]hexadeca-3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.

Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and

if swallowed.Very Toxic by inhalation

and if swallowed
|-
| Safety
| Wear suitable protective clothing and

eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.
[[Image:Saxsyn1.gif|Synthesis]]

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T14:08:41Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo
[11.3.0]hexadeca-3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.

Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and

if swallowed.Very Toxic by inhalation

and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.
[[Image:Saxsyn1.gif|Synthesis]]

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T14:07:55Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo
[11.3.0]hexadeca-3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.

Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.
[[Image:Saxsyn1.gif|Synthesis]]

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T14:02:20Z

Ak705: /* Synthesis */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo
[11.3.0]hexadeca-3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid. Insoluble
in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.
[[Image:Saxsyn1.gif|Synthesis]]

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

File:Saxsyn1.gif

2006-12-07T14:01:45Z

Ak705:

It:Saxitoxin

2006-12-07T14:01:14Z

Ak705: /* Synthesis */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo
[11.3.0]hexadeca-3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid. Insoluble
in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==
The first laboratory preparation of saxitoxin was carried out by Kishi at Harvard University in 1977. This synthesis relied on the condensation of a vinylogous carbamate with benzyloxyacetaldehyde and silicon tetraisopropoxide to produce an intermediate thiourea-ester which was converted to a thiourea-urea using standard methods. Cyclisation to provide the saxitoxin skeleton was accomplished readily by treatment with acid, the reaction proceeding via the intermediacy of an iminium ion. Functional group exchanges were then executed to achieve the first complete synthesis of racemic saxitoxin.

The second laboratory synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.

[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T13:55:47Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo
[11.3.0]hexadeca-3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid. Insoluble
in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Saxitoxin: A Chemical Weapon ==
<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T13:53:30Z

Ak705: /* References */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
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<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
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{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo
[11.3.0]hexadeca-3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid. Insoluble
in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm

2. https://www.cbwinfo.com/Biological/Toxins/Saxitoxin.html

3. https://www.globalsecurity.org/wmd/intro/bio_saxitoxin.htm

4. https://www.iscid.org/encyclopedia/Saxitoxin

5. https://www.cbwinfo.com/Biological/Toxins/SaxMarkush.html

6. https://www.sigmaaldrich.com

It:Saxitoxin

2006-12-07T13:48:17Z

Ak705: /* References */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo
[11.3.0]hexadeca-3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid. Insoluble
in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. https://www.chm.bris.ac.uk/motm/stx/saxi.htm
2.

It:Saxitoxin

2006-12-07T13:47:46Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo
[11.3.0]hexadeca-3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid. Insoluble
in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==
1. www.chm.bris.ac.uk/motm/stx/saxi.htm

It:Saxitoxin

2006-12-07T13:46:36Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo
[11.3.0]hexadeca-3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid. Insoluble
in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==

It:Saxitoxin

2006-12-07T13:46:13Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo
[11.3.0]hexadeca-3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2
(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in
lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==

It:Saxitoxin

2006-12-07T13:44:51Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)
N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==

It:Saxitoxin

2006-12-07T12:30:00Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

== References ==

It:Saxitoxin

2006-12-07T12:29:30Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |See table below
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

It:Saxitoxin

2006-12-07T12:29:05Z

Ak705: /* Related Compounds */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}
[[Image:Saxi.gif|Sax]]

File:Saxi.gif

2006-12-07T12:28:01Z

Ak705:

It:Saxitoxin

2006-12-07T12:24:28Z

Ak705: /* Related Compounds */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}

It:Saxitoxin

2006-12-07T12:21:30Z

Ak705: /* Related Compounds */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}

It:Saxitoxin

2006-12-07T12:21:07Z

Ak705: /* Related Compounds */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
| Gonyautoxin II
| H
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin III
| H
| H
| OSO3-
| OCONH2
|-
| Neosaxitoxin
| OH
| H
| H
| OCONH2
|-
| Gonyautoxin I
| OH
| OSO3-
| H
| OCONH2
|-
| Gonyautoxin IV
| OH
| H
| OSO3-
| OCONH2
|-
|}

It:Saxitoxin

2006-12-07T12:18:01Z

Ak705: /* Related Compounds */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chemical header}}|
|-align="center" colspan="1" bgcolor="#ffffff" |
|}

{|Name
| R1
| R2
| R3
| R4
|-
| Saxitoxin
| H
| H
| H
| OCONH2
|-
|
|
|
|
| OCONH2
|-
|
|
|
|
| OCONH2
|-
|
|
|
|
| OCONH2
|-
|
|
|
|
| OCONH2
|-
|
|
|
|
| OCONH2
|-
|}

It:Saxitoxin

2006-12-07T12:10:57Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

== Related Compounds ==

It:Saxitoxin

2006-12-07T12:00:34Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

It:Saxitoxin

2006-12-07T11:59:33Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

<jmol>
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<size>200</size>
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<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| [http://en.wikipedia.org/wiki/NFPA_704 NFPA 704]
| colspan="2" | {{NFPA 704 | Health=0 | Flammability=0 | Reactivity=0 | Other=}}
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| [http://en.wikipedia.org/wiki/Risk_and_Safety_Statements R/S statement]
| colspan="2" |
|-
| RIDADR
| colspan="2" |UN 3172 6.1/PG 1
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

It:Saxitoxin

2006-12-05T13:50:06Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

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<script>zoom 80; cpk on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |T+ (Very Toxic)
|-
| [http://en.wikipedia.org/wiki/NFPA_704 NFPA 704]
| colspan="2" | {{NFPA 704 | Health=0 | Flammability=0 | Reactivity=0 | Other=}}
|-
| Risk statement
| Very Toxic in contact with skin and if swallowed
Very Toxic by inhalation and if swallowed
|-
| Safety
| Wear suitable protective clothing and eye/face protection
|-
| [http://en.wikipedia.org/wiki/Risk_and_Safety_Statements R/S statement]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/RTECS RTECS] number
| colspan="2" |

|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

It:Saxitoxin

2006-12-05T12:45:14Z

Ak705:

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death. Saxitoxin binds to the sodium channels of neurones within the nervous system, rendering them inactive, and hence causing muscle paralysis which may eventually lead to death.

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<inlineContents>water.mol
HEADER NONAME 05-Dec-06 NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
ATOM 1 N 0 0.477 0.862 3.016 0.00 0.00 N+0
ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
ATOM 29 H 0 6.131 -0.041 -0.261 0.00 0.00 H+0
ATOM 30 H 0 -4.811 1.780 -0.400 0.00 0.00 H+0
ATOM 31 H 0 -3.993 2.889 -1.361 0.00 0.00 H+0
ATOM 32 H 0 -1.469 2.541 -1.755 0.00 0.00 H+0
ATOM 33 H 0 -0.497 -1.699 2.744 0.00 0.00 H+0
ATOM 34 H 0 -2.166 -1.066 2.659 0.00 0.00 H+0
ATOM 35 H 0 -1.004 -3.286 1.165 0.00 0.00 H+0
ATOM 36 H 0 -2.687 -2.678 1.110 0.00 0.00 H+0
ATOM 37 H 0 -2.371 -3.048 -1.390 0.00 0.00 H+0
ATOM 38 H 0 -0.089 -3.064 -0.969 0.00 0.00 H+0
CONECT 1 2 24 0 0 NONE 43
CONECT 2 1 18 3 0 NONE 44
CONECT 3 2 4 25 0 NONE 45
CONECT 4 3 5 6 11 NONE 46
CONECT 6 4 7 26 27 NONE 47
CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
END NONE 64
</inlineContents>
</jmolApplet>
</jmol>
{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| [http://en.wikipedia.org/wiki/Material_safety_data_sheet MSDS]
| colspan="2" |[http://www.sciencelab.com/xMSDS-Piperine-9926579#search=%22piperine%20MSDS%22 MSDS for Piperine] 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/NFPA_704 NFPA 704]
| colspan="2" | {{NFPA 704 | Health=0 | Flammability=0 | Reactivity=0 | Other=}}
|-
| [http://en.wikipedia.org/wiki/Flash_point Flash point]
| colspan="2" |? °C
|-
| [http://en.wikipedia.org/wiki/Risk_and_Safety_Statements R/S statement]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/RTECS RTECS] number
| colspan="2" |

|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

It:Saxitoxin

2006-12-05T12:39:32Z

Ak705: /* Effects of Saxitoxin */

Saxitoxin is the parent compound of a family of chemically related neurotoxins. It is mainly produced by marine dinoflagellates, which are then ingested by bivalve molluscs (shellfish) during filter feeding. It is the ingestion of these infected molluscs by humans that results in the condition known as paralytic shellfish poisoning (PSP), a severe illness which can result in death.

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TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 05-Dec-06 0 NONE 4
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ATOM 2 C 0 0.097 0.789 1.771 0.00 0.00 C+0
ATOM 3 N 0 0.574 1.656 0.805 0.00 0.00 N+0
ATOM 4 C 0 0.632 1.192 -0.578 0.00 0.00 C+0
ATOM 5 H 0 0.895 2.032 -1.221 0.00 0.00 H+0
ATOM 6 C 0 1.718 0.120 -0.696 0.00 0.00 C+0
ATOM 7 O 0 3.015 0.714 -0.428 0.00 0.00 O+0
ATOM 8 C 0 4.126 -0.045 -0.475 0.00 0.00 C+0
ATOM 9 N 0 5.331 0.506 -0.227 0.00 0.00 N+0
ATOM 10 O 0 4.043 -1.228 -0.742 0.00 0.00 O+0
ATOM 11 C 0 -0.687 0.607 -1.048 0.00 0.00 C+0
ATOM 12 H 0 -0.539 0.032 -1.962 0.00 0.00 H+0
ATOM 13 C 0 -1.391 -0.241 -0.001 0.00 0.00 C+0
ATOM 14 N 0 -2.772 0.254 0.009 0.00 0.00 N+0
ATOM 15 C 0 -2.837 1.348 -0.688 0.00 0.00 C+0
ATOM 16 N 0 -3.994 2.077 -0.830 0.00 0.00 N+0
ATOM 17 N 0 -1.644 1.711 -1.284 0.00 0.00 N+0
ATOM 18 N 0 -0.797 -0.158 1.335 0.00 0.00 N+0
ATOM 19 C 0 -1.280 -1.330 2.081 0.00 0.00 C+0
ATOM 20 C 0 -1.634 -2.406 1.032 0.00 0.00 C+0
ATOM 21 C 0 -1.373 -1.739 -0.357 0.00 0.00 C+0
ATOM 22 O 0 -2.400 -2.087 -1.288 0.00 0.00 O+0
ATOM 23 O 0 -0.086 -2.103 -0.860 0.00 0.00 O+0
ATOM 24 H 0 1.114 1.540 3.290 0.00 0.00 H+0
ATOM 25 H 0 0.863 2.552 1.041 0.00 0.00 H+0
ATOM 26 H 0 1.525 -0.673 0.027 0.00 0.00 H+0
ATOM 27 H 0 1.710 -0.296 -1.703 0.00 0.00 H+0
ATOM 28 H 0 5.397 1.450 -0.014 0.00 0.00 H+0
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CONECT 7 6 8 0 0 NONE 48
CONECT 8 7 9 10 0 NONE 49
CONECT 9 8 28 29 0 NONE 50
CONECT 10 8 0 0 0 NONE 51
CONECT 11 4 12 17 13 NONE 52
CONECT 13 11 21 14 18 NONE 53
CONECT 14 13 15 0 0 NONE 54
CONECT 15 14 16 17 0 NONE 55
CONECT 16 15 30 31 0 NONE 56
CONECT 17 15 11 32 0 NONE 57
CONECT 18 13 2 19 0 NONE 58
CONECT 19 18 20 33 34 NONE 59
CONECT 20 19 21 35 36 NONE 60
CONECT 21 20 13 22 23 NONE 61
CONECT 22 21 37 0 0 NONE 62
CONECT 23 21 38 0 0 NONE 63
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{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Saxitoxin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:saxitoxin.gif|Saxitoxin]]
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|(1R)-2c,15c-dihydroxy-7t-methyl-(1t,13t)-6-oxa-bicyclo[11.3.0]hexadeca-
3t,11t-dien-5-onebrefeldin A
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C10H17N7O4
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |N=C1N[C@@H](COC(N)=O)[C@H]3[C@]2(N=C(N)N3)N1CCC2(O)O
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |299.29
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |35523-89-8
|-
| colspan="1" |Type of Substance
| colspan="2" |heterocyclic
|-

! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility]
| colspan="2" |Freely soluble in water and methanol.
Limited solubility in ethanol and acetic acid.
Insoluble in lipid solvents
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K''a in water) 
| colspan="2" |8.24
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| [http://en.wikipedia.org/wiki/Material_safety_data_sheet MSDS]
| colspan="2" |[http://www.sciencelab.com/xMSDS-Piperine-9926579#search=%22piperine%20MSDS%22 MSDS for Piperine] 
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]s
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/NFPA_704 NFPA 704]
| colspan="2" | {{NFPA 704 | Health=0 | Flammability=0 | Reactivity=0 | Other=}}
|-
| [http://en.wikipedia.org/wiki/Flash_point Flash point]
| colspan="2" |? °C
|-
| [http://en.wikipedia.org/wiki/Risk_and_Safety_Statements R/S statement]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/RTECS RTECS] number
| colspan="2" |

|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|}

== Synthesis ==

The synthesis of saxitoxin was carried out by Jacobi and his collaborators whilst at Wesleyan University, Connecticut. The key step of Jacobi's synthesis of saxitoxin relied on formation of a benzylhydrazide intermediate, which was subjected to methyl glyoxylate hemimethyl acetal and a Lewis acid, in order to construct a highly reactive azomethine imine, which subsequently underwent an intramolecular 1,3-dipolar cycloaddition reaction, leading to an advanced tetracyclic intermediate. This was readily elaborated to accomplish a formal synthesis of the racemic natural product.
[[Image:Saxitoxinsynthesis.gif|Synthesis of Saxitoxin]]

== Paralytic Shellfish Poisoning (PSP) ==

After ingestion, absorption of toxins by the gastrointestinal tract is extremely fast. Symptoms typically begin to show around 10 minutes to an hour after initial exposure, but can be delayed a few hours depending on the dose received and the individual's natural defence. Symptoms begin with numbness or tingling of the lips, tongue, and fingertips, followed by numbness of the neck and extremities and general muscular incoordination. Nausea and vomiting may occur. Respiratory distress and flaccid muscular paralysis are the terminal stages and generally occur around 2-12 hours after initial intoxication. Death can result, due to respiratory paralysis. Clearance of the toxin is rapid and those surviving past 12-24 hours post exposure will usually recover. There are no known cases of inhalation exposure to saxitoxin by humans, but data from animal experiments suggest the entire syndrome is compressed and death may occur in minutes.

== Effects of Saxitoxin ==

Bivalve molluscs, the ingestion of which causes paralytic shellfish poisoning (PSP) in humans, show marked inter-species variation in their ability to accumulate paralytic shellfish toxins (PSTs) which has a neural basis. PSTs cause death in humans by blocking sodium channels in neurons. PSTs lead to death of toxin-sensitive molluscs, but it has been seen that some molluscs have gained a resistance to these PSTs. For example, softshell clams (''Mya arenaria'') from areas exposed to '''red tides''' have a higher resistance to PSTs, and accumulate these toxins at much greater rates than toxin-sensitive clams from unexposed areas. This apparent resistance is caused by the natural mutation of a single amino acid residue, thus causing a thousand-fold decrease in affinity at the saxitoxin-binding site in the sodium channel of resistant, but not sensitive, clams. Thus PSTs might act as potent natural selection agents, leading to greater toxin resistance in clam populations and increased risk of PSP in humans.

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2006-12-05T12:25:54Z

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