==Sibutramine==
{| class="toccolours" border="1" style="fix: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
|-
|align="center" colspan="3" bgcolor="white"|
[[Image:sibutramine.gif]]
|-
! {{chembox header}} colspan="3"| 3D structure
|-
| align="center" colspan="3" bgcolor="#ffffff" | <jmol>

<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 100; bns on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER Sibutramine NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 20-Oct-06 0 NONE 4
ATOM 1 Cl 0 4.921 -0.468 -0.279 0.00 0.00 Cl+0
ATOM 2 C 0 3.242 -0.131 0.004 0.00 0.00 C+0
ATOM 3 C 0 2.815 0.248 1.264 0.00 0.00 C+0
ATOM 4 C 0 1.477 0.515 1.489 0.00 0.00 C+0
ATOM 5 C 0 0.567 0.404 0.455 0.00 0.00 C+0
ATOM 6 C 0 -0.891 0.695 0.700 0.00 0.00 C+0
ATOM 7 C 0 -1.777 0.347 -0.498 0.00 0.00 C+0
ATOM 8 N 0 -1.347 1.126 -1.667 0.00 0.00 N+0
ATOM 9 C 0 -1.872 0.433 -2.852 0.00 0.00 C+0
ATOM 10 C 0 -2.041 2.418 -1.591 0.00 0.00 C+0
ATOM 11 C 0 -1.653 -1.146 -0.807 0.00 0.00 C+0
ATOM 12 C 0 -2.199 -1.957 0.370 0.00 0.00 C+0
ATOM 13 C 0 -3.661 -1.577 0.617 0.00 0.00 C+0
ATOM 14 C 0 -2.108 -3.450 0.047 0.00 0.00 C+0
ATOM 15 C 0 -1.414 0.139 2.035 0.00 0.00 C+0
ATOM 16 C 0 -2.210 1.447 2.178 0.00 0.00 C+0
ATOM 17 C 0 -1.151 2.099 1.271 0.00 0.00 C+0
ATOM 18 C 0 0.993 0.025 -0.805 0.00 0.00 C+0
ATOM 19 C 0 2.331 -0.237 -1.032 0.00 0.00 C+0
ATOM 20 H 0 3.526 0.334 2.072 0.00 0.00 H+0
ATOM 21 H 0 1.144 0.811 2.472 0.00 0.00 H+0
ATOM 22 H 0 -2.814 0.585 -0.264 0.00 0.00 H+0
ATOM 23 H 0 -2.924 0.194 -2.696 0.00 0.00 H+0
ATOM 24 H 0 -1.771 1.079 -3.724 0.00 0.00 H+0
ATOM 25 H 0 -1.310 -0.486 -3.013 0.00 0.00 H+0
ATOM 26 H 0 -1.431 3.126 -1.030 0.00 0.00 H+0
ATOM 27 H 0 -2.207 2.801 -2.599 0.00 0.00 H+0
ATOM 28 H 0 -3.000 2.287 -1.090 0.00 0.00 H+0
ATOM 29 H 0 -2.225 -1.380 -1.705 0.00 0.00 H+0
ATOM 30 H 0 -0.605 -1.399 -0.967 0.00 0.00 H+0
ATOM 31 H 0 -1.612 -1.742 1.263 0.00 0.00 H+0
ATOM 32 H 0 -4.261 -1.862 -0.247 0.00 0.00 H+0
ATOM 33 H 0 -4.027 -2.098 1.502 0.00 0.00 H+0
ATOM 34 H 0 -3.735 -0.501 0.773 0.00 0.00 H+0
ATOM 35 H 0 -1.067 -3.721 -0.128 0.00 0.00 H+0
ATOM 36 H 0 -2.497 -4.028 0.886 0.00 0.00 H+0
ATOM 37 H 0 -2.695 -3.665 -0.845 0.00 0.00 H+0
ATOM 38 H 0 -2.043 -0.745 1.923 0.00 0.00 H+0
ATOM 39 H 0 -0.638 0.015 2.791 0.00 0.00 H+0
ATOM 40 H 0 -3.203 1.405 1.729 0.00 0.00 H+0
ATOM 41 H 0 -2.221 1.843 3.194 0.00 0.00 H+0
ATOM 42 H 0 -0.303 2.512 1.817 0.00 0.00 H+0
ATOM 43 H 0 -1.568 2.797 0.545 0.00 0.00 H+0
ATOM 44 H 0 0.281 -0.061 -1.612 0.00 0.00 H+0
ATOM 45 H 0 2.664 -0.533 -2.016 0.00 0.00 H+0
CONECT 1 2 0 0 0 NONE 50
CONECT 2 1 19 3 0 NONE 51
CONECT 3 2 4 20 0 NONE 52
CONECT 4 3 5 21 0 NONE 53
CONECT 5 4 6 18 0 NONE 54
CONECT 6 5 17 7 15 NONE 55
CONECT 7 6 8 11 22 NONE 56
CONECT 8 7 9 10 0 NONE 57
CONECT 9 8 23 24 25 NONE 58
CONECT 10 8 26 27 28 NONE 59
CONECT 11 7 12 29 30 NONE 60
CONECT 12 11 13 14 31 NONE 61
CONECT 13 12 32 33 34 NONE 62
CONECT 14 12 35 36 37 NONE 63
CONECT 15 6 16 38 39 NONE 64
CONECT 16 15 17 40 41 NONE 65
CONECT 17 16 6 42 43 NONE 66
CONECT 18 5 19 44 0 NONE 67
CONECT 19 18 2 45 0 NONE 68
END NONE 69
</inlineContents>
</jmolApplet>
</jmol>

|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2" | {1-[1-(4-chloro-phenyl)-cyclobutyl]-3-methyl-butyl}-dimethyl-amine
|-
| colspan="1" |Commercial names
| colspan="2" | MERIDIA (sibutramine hydrochloride monohydrate)
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C17H26Cl N (MERIDIA: C17H29Cl2NO)
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |279.85 (MERIDIA: 334.33)
|-
| colspan="1" |Appearance
| colspan="2" |White to cream crystalline powder
|-
|colspan="1" |Beilstein Registry number
| colspan="2" |
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |
|-
! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility] in [ http://en.wikipedia.org/wiki/Water_%28molecule%29 Water_(molecule)| Solubility in Water
| colspan="2" | 2.9 mg/mL in pH 5.2 water
|-
| Other solvents
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Melting_point Melting point]
| colspan="2" | 191-192°C
|-
| [http://en.wikipedia.org/wiki/Boiling_point Boiling point]
| colspan="2" |
|-
! {{chembox header}} colspan="3"| Structure
|-
| [http://en.wikipedia.org/wiki/Crystal_structure Crystal structure] 
| colspan="2"|
|-
| [http://en.wikipedia.org/wiki/Dipole#Molecular_dipoles Dipole moment]
| colspan="2" |
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| [http://en.wikipedia.org/wiki/Material_safety_data_sheet MSDS]
| colspan="2" |
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/NFPA_704 NFPA 704]
| colspan="2" |
|-
| [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" | Spectral data
|-

| NMR
|align="center" colspan="3" bgcolor="white"|
[[Image:nmrsibutramine.gif]]
|-

| IR
|align="center" colspan="3" bgcolor="white"|
[[Image:Table.JPG]]
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|-
| {{chembox header}} colspan="3"| Except where noted otherwise, data are given for materials in their [http://en.wikipedia.org/wiki/Standard_state standard state (at 25 °C, 100 kPa)] [http://en.wikipedia.org/wiki/Wikipedia:Chemical_infobox Infobox disclaimer and references]]
|-
|}

 

=='''How is Sibutramine synthesized?'''==
[[Image:synthesissibu.gif|right|100|Reaction scheme showing Sibutramine synthesis]] 
The reaction scheme shown on the right gives an overview of how Sibutramine is synthesized1. Known methods for preparation of crucial intermediate in the synthesis of ''1-1-(4-chlorophenyl)-1-cyanocyclobutane'' consist of cycloalkylation of 4-chlorophenylacetonitrile with 1,3-dibromopropane in the presence of such base/solvent systems as: NaH/DMSO/ether, solid KOH/DMSO/ether, solid KOH/toluene/quaternary ammonium salt as a catalyst (solid - liquid phase transfer catalysis, PTC). All of them are inconvenient for large scale applications. On the other hand, it is now commonly accepted, that liquid-liquid PTC (conc. aq. solution of NaOH as a base) is the best practical procedure for alkylation of carbanions of arylacetonitriles and their derivatives. However, with 1,3-dibromopropane under typical PTC conditions (50% NaOH aq. as a base) yields of 1-aryl-1-cyanocyclobutanes are low, b-elimination of HBr from the alkylating agent is often observed, leading to mono- and diallylated arylacetonitriles as by product, which are difficult to separate.

It was experimentally observed that a simple change of 50% NaOH for 60% KOH overcomes all the difficulties mentioned above. Cycloalkylation of 4-chlorophenylacetonitrile with 1,3-dibromopropane carried out in the presence of 60% KOH and tetrabutylammonium bromide (TBAB) as a catalyst in toluene as a solvent proceeds in high yield, b-elimination of HBr from the alkylating agent practically does not proceed and isolation of ''1-1-(4-chlorophenyl)-1-cyanocyclobutane'' is pretty simple. This process was performed on a 10 mol scale, with the yields exceeding 70%.
 
 
 
 
 
== '''How does Sibutramine aid in weight loss?''' ==
Sibutramine pills5: 
[[Image:sibutramine.jpg|60|Sibutramine pills]] 
Sibutramine primarily works by increasing feelings of satiety and reducing appetite. It is recommended to patients with a BMI of 30kg m-2 or more for aiding weight loss by reducing appetite and increasing satiety. 
It increases blood pressure in some patients4 and therefore blood pressure must be monitored during treatment to ensure that it does not become dangerously high. 
However, the weight loss as a result of using Sibutramine does not come without a price. Side effects of Sibutramine include dry mouth, constipation and insomnia. Less common side effects include headache, increased sweating, increased blood pressure and increased heart rate. Of these, the issue of increased blood pressure is the most concerning, but it is less common and since patients with obesity are regularly monitored by their doctors for changes in blood pressure, this risk is mitigated somewhat2. In addition, Sibutramine should not be prescribed for people with a history of coronary artery disease, congestive heart failure, arrhythmias or stroke, as it may dangerously increase the individual's heart rate and/or blood pressure. 
 
=='''Working principles behind Sibutramine''' ==
[[Image:neuro.gif|right|100|Working principle behind Sibutramine]]
Sibutramine (commercially known as Meridia®) is an equipotent serotonin and norepinephrine reuptake inhibitor (SNRI), which means it has an equal effect on serotonin (a brain neurotransmitter which generally promotes a calming feeling) and norepinephrine (a stimulant). The diagram on the right shows how this is brought about6. Research indicates that these brain chemicals have an effect on appetite and satiety. 

Animals given sibutramine have shown an increase in metabolic rate3, but human studies have not been conclusive. The reasons for the difference between animals and humans is not clear but may be due to the small number of subjects tested and the small effect of the drug on energy expenditure. However, even small increases in thermogenesis could be clinically significant in weight loss and weight maintenance. (Thermogenesis refers to increased fat loss through raising the body's core temperature or through an increased caloric use as a result of an heightened energy/metabolic state) 
 
=='''References''' ==
1) [http://www.science24.com/paper/6574 Science24.com/confernces] 
2) ''The effect of sibutramine-assisted weight loss in men with obstructive sleep apnoea'',International Journal of Obesity, 2 May 2006 
3) Malhotra A, White DP. Obstructive sleep apnoea. Lancet 2002; 360: 237–245 
4) Kim SH, Lee YM, Jee SH, Nam CM. Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 2003; 11: 1116–1123 
5) [http://www.myelectronicpharmacy.com My electronic pharmacy] 
6) [http://images.google.co.uk/imgres?imgurl=http://www.weightloss-news.com/graphics.htg/mermov.gif&imgrefurl=http://www.obesity-news.com/merfaq.htm&h=184&w=300&sz=40&hl=en&start=1&tbnid=ieLgEWX8ICsvJM:&tbnh=71&tbnw=116&prev=/images%3Fq%3Dsibutramine%26ndsp%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN Obesity Meds and Research News] 
7) http://www.rxlist.com/cgi/generic/sibutramine.htm 
8) http://www.chemsoc.org/ExemplarChem/entries/2003/imperial_Rowlands/index.html

File:Table.JPG

2006-10-30T14:39:55Z

Ylt05:

It:Sibutramine

2006-10-30T14:37:13Z

Ylt05:

==Sibutramine==
{| class="toccolours" border="1" style="fix: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
|-
|align="center" colspan="3" bgcolor="white"|
[[Image:sibutramine.gif]]
|-
! {{chembox header}} colspan="3"| 3D structure
|-
| align="center" colspan="3" bgcolor="#ffffff" | <jmol>

<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 100; bns on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER Sibutramine NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 20-Oct-06 0 NONE 4
ATOM 1 Cl 0 4.921 -0.468 -0.279 0.00 0.00 Cl+0
ATOM 2 C 0 3.242 -0.131 0.004 0.00 0.00 C+0
ATOM 3 C 0 2.815 0.248 1.264 0.00 0.00 C+0
ATOM 4 C 0 1.477 0.515 1.489 0.00 0.00 C+0
ATOM 5 C 0 0.567 0.404 0.455 0.00 0.00 C+0
ATOM 6 C 0 -0.891 0.695 0.700 0.00 0.00 C+0
ATOM 7 C 0 -1.777 0.347 -0.498 0.00 0.00 C+0
ATOM 8 N 0 -1.347 1.126 -1.667 0.00 0.00 N+0
ATOM 9 C 0 -1.872 0.433 -2.852 0.00 0.00 C+0
ATOM 10 C 0 -2.041 2.418 -1.591 0.00 0.00 C+0
ATOM 11 C 0 -1.653 -1.146 -0.807 0.00 0.00 C+0
ATOM 12 C 0 -2.199 -1.957 0.370 0.00 0.00 C+0
ATOM 13 C 0 -3.661 -1.577 0.617 0.00 0.00 C+0
ATOM 14 C 0 -2.108 -3.450 0.047 0.00 0.00 C+0
ATOM 15 C 0 -1.414 0.139 2.035 0.00 0.00 C+0
ATOM 16 C 0 -2.210 1.447 2.178 0.00 0.00 C+0
ATOM 17 C 0 -1.151 2.099 1.271 0.00 0.00 C+0
ATOM 18 C 0 0.993 0.025 -0.805 0.00 0.00 C+0
ATOM 19 C 0 2.331 -0.237 -1.032 0.00 0.00 C+0
ATOM 20 H 0 3.526 0.334 2.072 0.00 0.00 H+0
ATOM 21 H 0 1.144 0.811 2.472 0.00 0.00 H+0
ATOM 22 H 0 -2.814 0.585 -0.264 0.00 0.00 H+0
ATOM 23 H 0 -2.924 0.194 -2.696 0.00 0.00 H+0
ATOM 24 H 0 -1.771 1.079 -3.724 0.00 0.00 H+0
ATOM 25 H 0 -1.310 -0.486 -3.013 0.00 0.00 H+0
ATOM 26 H 0 -1.431 3.126 -1.030 0.00 0.00 H+0
ATOM 27 H 0 -2.207 2.801 -2.599 0.00 0.00 H+0
ATOM 28 H 0 -3.000 2.287 -1.090 0.00 0.00 H+0
ATOM 29 H 0 -2.225 -1.380 -1.705 0.00 0.00 H+0
ATOM 30 H 0 -0.605 -1.399 -0.967 0.00 0.00 H+0
ATOM 31 H 0 -1.612 -1.742 1.263 0.00 0.00 H+0
ATOM 32 H 0 -4.261 -1.862 -0.247 0.00 0.00 H+0
ATOM 33 H 0 -4.027 -2.098 1.502 0.00 0.00 H+0
ATOM 34 H 0 -3.735 -0.501 0.773 0.00 0.00 H+0
ATOM 35 H 0 -1.067 -3.721 -0.128 0.00 0.00 H+0
ATOM 36 H 0 -2.497 -4.028 0.886 0.00 0.00 H+0
ATOM 37 H 0 -2.695 -3.665 -0.845 0.00 0.00 H+0
ATOM 38 H 0 -2.043 -0.745 1.923 0.00 0.00 H+0
ATOM 39 H 0 -0.638 0.015 2.791 0.00 0.00 H+0
ATOM 40 H 0 -3.203 1.405 1.729 0.00 0.00 H+0
ATOM 41 H 0 -2.221 1.843 3.194 0.00 0.00 H+0
ATOM 42 H 0 -0.303 2.512 1.817 0.00 0.00 H+0
ATOM 43 H 0 -1.568 2.797 0.545 0.00 0.00 H+0
ATOM 44 H 0 0.281 -0.061 -1.612 0.00 0.00 H+0
ATOM 45 H 0 2.664 -0.533 -2.016 0.00 0.00 H+0
CONECT 1 2 0 0 0 NONE 50
CONECT 2 1 19 3 0 NONE 51
CONECT 3 2 4 20 0 NONE 52
CONECT 4 3 5 21 0 NONE 53
CONECT 5 4 6 18 0 NONE 54
CONECT 6 5 17 7 15 NONE 55
CONECT 7 6 8 11 22 NONE 56
CONECT 8 7 9 10 0 NONE 57
CONECT 9 8 23 24 25 NONE 58
CONECT 10 8 26 27 28 NONE 59
CONECT 11 7 12 29 30 NONE 60
CONECT 12 11 13 14 31 NONE 61
CONECT 13 12 32 33 34 NONE 62
CONECT 14 12 35 36 37 NONE 63
CONECT 15 6 16 38 39 NONE 64
CONECT 16 15 17 40 41 NONE 65
CONECT 17 16 6 42 43 NONE 66
CONECT 18 5 19 44 0 NONE 67
CONECT 19 18 2 45 0 NONE 68
END NONE 69
</inlineContents>
</jmolApplet>
</jmol>

|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2" | {1-[1-(4-chloro-phenyl)-cyclobutyl]-3-methyl-butyl}-dimethyl-amine
|-
| colspan="1" |Commercial names
| colspan="2" | MERIDIA (sibutramine hydrochloride monohydrate)
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C17H26Cl N (MERIDIA: C17H29Cl2NO)
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |279.85 (MERIDIA: 334.33)
|-
| colspan="1" |Appearance
| colspan="2" |White to cream crystalline powder
|-
|colspan="1" |Beilstein Registry number
| colspan="2" |
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |
|-
! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility] in [ http://en.wikipedia.org/wiki/Water_%28molecule%29 Water_(molecule)| Solubility in Water
| colspan="2" | 2.9 mg/mL in pH 5.2 water
|-
| Other solvents
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Melting_point Melting point]
| colspan="2" | 191-192°C
|-
| [http://en.wikipedia.org/wiki/Boiling_point Boiling point]
| colspan="2" |
|-
! {{chembox header}} colspan="3"| Structure
|-
| [http://en.wikipedia.org/wiki/Crystal_structure Crystal structure] 
| colspan="2"|
|-
| [http://en.wikipedia.org/wiki/Dipole#Molecular_dipoles Dipole moment]
| colspan="2" |
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| [http://en.wikipedia.org/wiki/Material_safety_data_sheet MSDS]
| colspan="2" |
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/NFPA_704 NFPA 704]
| colspan="2" |
|-
| [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" | Spectral data
|-

| NMR
|align="center" colspan="3" bgcolor="white"|
[[Image:nmrsibutramine.gif]]
|-

| IR
|align="center" colspan="3" bgcolor="white"|
[[Image:table.gif]]
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|-
| {{chembox header}} colspan="3"| Except where noted otherwise, data are given for materials in their [http://en.wikipedia.org/wiki/Standard_state standard state (at 25 °C, 100 kPa)] [http://en.wikipedia.org/wiki/Wikipedia:Chemical_infobox Infobox disclaimer and references]]
|-
|}

 

=='''How is Sibutramine synthesized?'''==
[[Image:synthesissibu.gif|right|100|Reaction scheme showing Sibutramine synthesis]] 
The reaction scheme shown on the right gives an overview of how Sibutramine is synthesized1. Known methods for preparation of crucial intermediate in the synthesis of ''1-1-(4-chlorophenyl)-1-cyanocyclobutane'' consist of cycloalkylation of 4-chlorophenylacetonitrile with 1,3-dibromopropane in the presence of such base/solvent systems as: NaH/DMSO/ether, solid KOH/DMSO/ether, solid KOH/toluene/quaternary ammonium salt as a catalyst (solid - liquid phase transfer catalysis, PTC). All of them are inconvenient for large scale applications. On the other hand, it is now commonly accepted, that liquid-liquid PTC (conc. aq. solution of NaOH as a base) is the best practical procedure for alkylation of carbanions of arylacetonitriles and their derivatives. However, with 1,3-dibromopropane under typical PTC conditions (50% NaOH aq. as a base) yields of 1-aryl-1-cyanocyclobutanes are low, b-elimination of HBr from the alkylating agent is often observed, leading to mono- and diallylated arylacetonitriles as by product, which are difficult to separate.

It was experimentally observed that a simple change of 50% NaOH for 60% KOH overcomes all the difficulties mentioned above. Cycloalkylation of 4-chlorophenylacetonitrile with 1,3-dibromopropane carried out in the presence of 60% KOH and tetrabutylammonium bromide (TBAB) as a catalyst in toluene as a solvent proceeds in high yield, b-elimination of HBr from the alkylating agent practically does not proceed and isolation of ''1-1-(4-chlorophenyl)-1-cyanocyclobutane'' is pretty simple. This process was performed on a 10 mol scale, with the yields exceeding 70%.
 
 
 
 
 
== '''How does Sibutramine aid in weight loss?''' ==
Sibutramine pills5: 
[[Image:sibutramine.jpg|60|Sibutramine pills]] 
Sibutramine primarily works by increasing feelings of satiety and reducing appetite. It is recommended to patients with a BMI of 30kg m-2 or more for aiding weight loss by reducing appetite and increasing satiety. 
It increases blood pressure in some patients4 and therefore blood pressure must be monitored during treatment to ensure that it does not become dangerously high. 
However, the weight loss as a result of using Sibutramine does not come without a price. Side effects of Sibutramine include dry mouth, constipation and insomnia. Less common side effects include headache, increased sweating, increased blood pressure and increased heart rate. Of these, the issue of increased blood pressure is the most concerning, but it is less common and since patients with obesity are regularly monitored by their doctors for changes in blood pressure, this risk is mitigated somewhat2. In addition, Sibutramine should not be prescribed for people with a history of coronary artery disease, congestive heart failure, arrhythmias or stroke, as it may dangerously increase the individual's heart rate and/or blood pressure. 
 
=='''Working principles behind Sibutramine''' ==
[[Image:neuro.gif|right|100|Working principle behind Sibutramine]]
Sibutramine (commercially known as Meridia®) is an equipotent serotonin and norepinephrine reuptake inhibitor (SNRI), which means it has an equal effect on serotonin (a brain neurotransmitter which generally promotes a calming feeling) and norepinephrine (a stimulant). The diagram on the right shows how this is brought about6. Research indicates that these brain chemicals have an effect on appetite and satiety. 

Animals given sibutramine have shown an increase in metabolic rate3, but human studies have not been conclusive. The reasons for the difference between animals and humans is not clear but may be due to the small number of subjects tested and the small effect of the drug on energy expenditure. However, even small increases in thermogenesis could be clinically significant in weight loss and weight maintenance. (Thermogenesis refers to increased fat loss through raising the body's core temperature or through an increased caloric use as a result of an heightened energy/metabolic state) 
 
=='''References''' ==
1) [http://www.science24.com/paper/6574 Science24.com/confernces] 
2) ''The effect of sibutramine-assisted weight loss in men with obstructive sleep apnoea'',International Journal of Obesity, 2 May 2006 
3) Malhotra A, White DP. Obstructive sleep apnoea. Lancet 2002; 360: 237–245 
4) Kim SH, Lee YM, Jee SH, Nam CM. Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 2003; 11: 1116–1123 
5) [http://www.myelectronicpharmacy.com My electronic pharmacy] 
6) [http://images.google.co.uk/imgres?imgurl=http://www.weightloss-news.com/graphics.htg/mermov.gif&imgrefurl=http://www.obesity-news.com/merfaq.htm&h=184&w=300&sz=40&hl=en&start=1&tbnid=ieLgEWX8ICsvJM:&tbnh=71&tbnw=116&prev=/images%3Fq%3Dsibutramine%26ndsp%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN Obesity Meds and Research News] 
7) http://www.rxlist.com/cgi/generic/sibutramine.htm 
8) http://www.chemsoc.org/ExemplarChem/entries/2003/imperial_Rowlands/index.html

It:Sibutramine

2006-10-30T14:20:45Z

Ylt05:

==Sibutramine==
{| class="toccolours" border="1" style="fix: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
|-
|align="center" colspan="3" bgcolor="white"|
[[Image:sibutramine.gif]]
|-
! {{chembox header}} colspan="3"| 3D structure
|-
| align="center" colspan="3" bgcolor="#ffffff" | <jmol>

<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 100; bns on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER Sibutramine NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 20-Oct-06 0 NONE 4
ATOM 1 Cl 0 4.921 -0.468 -0.279 0.00 0.00 Cl+0
ATOM 2 C 0 3.242 -0.131 0.004 0.00 0.00 C+0
ATOM 3 C 0 2.815 0.248 1.264 0.00 0.00 C+0
ATOM 4 C 0 1.477 0.515 1.489 0.00 0.00 C+0
ATOM 5 C 0 0.567 0.404 0.455 0.00 0.00 C+0
ATOM 6 C 0 -0.891 0.695 0.700 0.00 0.00 C+0
ATOM 7 C 0 -1.777 0.347 -0.498 0.00 0.00 C+0
ATOM 8 N 0 -1.347 1.126 -1.667 0.00 0.00 N+0
ATOM 9 C 0 -1.872 0.433 -2.852 0.00 0.00 C+0
ATOM 10 C 0 -2.041 2.418 -1.591 0.00 0.00 C+0
ATOM 11 C 0 -1.653 -1.146 -0.807 0.00 0.00 C+0
ATOM 12 C 0 -2.199 -1.957 0.370 0.00 0.00 C+0
ATOM 13 C 0 -3.661 -1.577 0.617 0.00 0.00 C+0
ATOM 14 C 0 -2.108 -3.450 0.047 0.00 0.00 C+0
ATOM 15 C 0 -1.414 0.139 2.035 0.00 0.00 C+0
ATOM 16 C 0 -2.210 1.447 2.178 0.00 0.00 C+0
ATOM 17 C 0 -1.151 2.099 1.271 0.00 0.00 C+0
ATOM 18 C 0 0.993 0.025 -0.805 0.00 0.00 C+0
ATOM 19 C 0 2.331 -0.237 -1.032 0.00 0.00 C+0
ATOM 20 H 0 3.526 0.334 2.072 0.00 0.00 H+0
ATOM 21 H 0 1.144 0.811 2.472 0.00 0.00 H+0
ATOM 22 H 0 -2.814 0.585 -0.264 0.00 0.00 H+0
ATOM 23 H 0 -2.924 0.194 -2.696 0.00 0.00 H+0
ATOM 24 H 0 -1.771 1.079 -3.724 0.00 0.00 H+0
ATOM 25 H 0 -1.310 -0.486 -3.013 0.00 0.00 H+0
ATOM 26 H 0 -1.431 3.126 -1.030 0.00 0.00 H+0
ATOM 27 H 0 -2.207 2.801 -2.599 0.00 0.00 H+0
ATOM 28 H 0 -3.000 2.287 -1.090 0.00 0.00 H+0
ATOM 29 H 0 -2.225 -1.380 -1.705 0.00 0.00 H+0
ATOM 30 H 0 -0.605 -1.399 -0.967 0.00 0.00 H+0
ATOM 31 H 0 -1.612 -1.742 1.263 0.00 0.00 H+0
ATOM 32 H 0 -4.261 -1.862 -0.247 0.00 0.00 H+0
ATOM 33 H 0 -4.027 -2.098 1.502 0.00 0.00 H+0
ATOM 34 H 0 -3.735 -0.501 0.773 0.00 0.00 H+0
ATOM 35 H 0 -1.067 -3.721 -0.128 0.00 0.00 H+0
ATOM 36 H 0 -2.497 -4.028 0.886 0.00 0.00 H+0
ATOM 37 H 0 -2.695 -3.665 -0.845 0.00 0.00 H+0
ATOM 38 H 0 -2.043 -0.745 1.923 0.00 0.00 H+0
ATOM 39 H 0 -0.638 0.015 2.791 0.00 0.00 H+0
ATOM 40 H 0 -3.203 1.405 1.729 0.00 0.00 H+0
ATOM 41 H 0 -2.221 1.843 3.194 0.00 0.00 H+0
ATOM 42 H 0 -0.303 2.512 1.817 0.00 0.00 H+0
ATOM 43 H 0 -1.568 2.797 0.545 0.00 0.00 H+0
ATOM 44 H 0 0.281 -0.061 -1.612 0.00 0.00 H+0
ATOM 45 H 0 2.664 -0.533 -2.016 0.00 0.00 H+0
CONECT 1 2 0 0 0 NONE 50
CONECT 2 1 19 3 0 NONE 51
CONECT 3 2 4 20 0 NONE 52
CONECT 4 3 5 21 0 NONE 53
CONECT 5 4 6 18 0 NONE 54
CONECT 6 5 17 7 15 NONE 55
CONECT 7 6 8 11 22 NONE 56
CONECT 8 7 9 10 0 NONE 57
CONECT 9 8 23 24 25 NONE 58
CONECT 10 8 26 27 28 NONE 59
CONECT 11 7 12 29 30 NONE 60
CONECT 12 11 13 14 31 NONE 61
CONECT 13 12 32 33 34 NONE 62
CONECT 14 12 35 36 37 NONE 63
CONECT 15 6 16 38 39 NONE 64
CONECT 16 15 17 40 41 NONE 65
CONECT 17 16 6 42 43 NONE 66
CONECT 18 5 19 44 0 NONE 67
CONECT 19 18 2 45 0 NONE 68
END NONE 69
</inlineContents>
</jmolApplet>
</jmol>

|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2" | {1-[1-(4-chloro-phenyl)-cyclobutyl]-3-methyl-butyl}-dimethyl-amine
|-
| colspan="1" |Commercial names
| colspan="2" | MERIDIA (sibutramine hydrochloride monohydrate)
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C17H26Cl N (MERIDIA: C17H29Cl2NO)
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |279.85 (MERIDIA: 334.33)
|-
| colspan="1" |Appearance
| colspan="2" |White to cream crystalline powder
|-
|colspan="1" |Beilstein Registry number
| colspan="2" |
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |
|-
! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility] in [ http://en.wikipedia.org/wiki/Water_%28molecule%29 Water_(molecule)| Solubility in Water
| colspan="2" | 2.9 mg/mL in pH 5.2 water
|-
| Other solvents
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Melting_point Melting point]
| colspan="2" | 191-192°C
|-
| [http://en.wikipedia.org/wiki/Boiling_point Boiling point]
| colspan="2" |
|-
! {{chembox header}} colspan="3"| Structure
|-
| [http://en.wikipedia.org/wiki/Crystal_structure Crystal structure] 
| colspan="2"|
|-
| [http://en.wikipedia.org/wiki/Dipole#Molecular_dipoles Dipole moment]
| colspan="2" |
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| [http://en.wikipedia.org/wiki/Material_safety_data_sheet MSDS]
| colspan="2" |
|-
| Main [http://en.wikipedia.org/wiki/Worker_safety_and_health hazard]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/NFPA_704 NFPA 704]
| colspan="2" |
|-
| [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" | Spectral data
|-

| NMR
|align="center" colspan="3" bgcolor="white"|
[[Image:nmrsibutramine.gif]]
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|-
| {{chembox header}} colspan="3"| Except where noted otherwise, data are given for materials in their [http://en.wikipedia.org/wiki/Standard_state standard state (at 25 °C, 100 kPa)] [http://en.wikipedia.org/wiki/Wikipedia:Chemical_infobox Infobox disclaimer and references]]
|-
|}

 

=='''How is Sibutramine synthesized?'''==
[[Image:synthesissibu.gif|right|100|Reaction scheme showing Sibutramine synthesis]] 
The reaction scheme shown on the right gives an overview of how Sibutramine is synthesized1. Known methods for preparation of crucial intermediate in the synthesis of ''1-1-(4-chlorophenyl)-1-cyanocyclobutane'' consist of cycloalkylation of 4-chlorophenylacetonitrile with 1,3-dibromopropane in the presence of such base/solvent systems as: NaH/DMSO/ether, solid KOH/DMSO/ether, solid KOH/toluene/quaternary ammonium salt as a catalyst (solid - liquid phase transfer catalysis, PTC). All of them are inconvenient for large scale applications. On the other hand, it is now commonly accepted, that liquid-liquid PTC (conc. aq. solution of NaOH as a base) is the best practical procedure for alkylation of carbanions of arylacetonitriles and their derivatives. However, with 1,3-dibromopropane under typical PTC conditions (50% NaOH aq. as a base) yields of 1-aryl-1-cyanocyclobutanes are low, b-elimination of HBr from the alkylating agent is often observed, leading to mono- and diallylated arylacetonitriles as by product, which are difficult to separate.

It was experimentally observed that a simple change of 50% NaOH for 60% KOH overcomes all the difficulties mentioned above. Cycloalkylation of 4-chlorophenylacetonitrile with 1,3-dibromopropane carried out in the presence of 60% KOH and tetrabutylammonium bromide (TBAB) as a catalyst in toluene as a solvent proceeds in high yield, b-elimination of HBr from the alkylating agent practically does not proceed and isolation of ''1-1-(4-chlorophenyl)-1-cyanocyclobutane'' is pretty simple. This process was performed on a 10 mol scale, with the yields exceeding 70%.
 
 
 
 
 
== '''How does Sibutramine aid in weight loss?''' ==
Sibutramine pills5: 
[[Image:sibutramine.jpg|60|Sibutramine pills]] 
Sibutramine primarily works by increasing feelings of satiety and reducing appetite. It is recommended to patients with a BMI of 30kg m-2 or more for aiding weight loss by reducing appetite and increasing satiety. 
It increases blood pressure in some patients4 and therefore blood pressure must be monitored during treatment to ensure that it does not become dangerously high. 
However, the weight loss as a result of using Sibutramine does not come without a price. Side effects of Sibutramine include dry mouth, constipation and insomnia. Less common side effects include headache, increased sweating, increased blood pressure and increased heart rate. Of these, the issue of increased blood pressure is the most concerning, but it is less common and since patients with obesity are regularly monitored by their doctors for changes in blood pressure, this risk is mitigated somewhat2. In addition, Sibutramine should not be prescribed for people with a history of coronary artery disease, congestive heart failure, arrhythmias or stroke, as it may dangerously increase the individual's heart rate and/or blood pressure. 
 
=='''Working principles behind Sibutramine''' ==
[[Image:neuro.gif|right|100|Working principle behind Sibutramine]]
Sibutramine (commercially known as Meridia®) is an equipotent serotonin and norepinephrine reuptake inhibitor (SNRI), which means it has an equal effect on serotonin (a brain neurotransmitter which generally promotes a calming feeling) and norepinephrine (a stimulant). The diagram on the right shows how this is brought about6. Research indicates that these brain chemicals have an effect on appetite and satiety. 

Animals given sibutramine have shown an increase in metabolic rate3, but human studies have not been conclusive. The reasons for the difference between animals and humans is not clear but may be due to the small number of subjects tested and the small effect of the drug on energy expenditure. However, even small increases in thermogenesis could be clinically significant in weight loss and weight maintenance. (Thermogenesis refers to increased fat loss through raising the body's core temperature or through an increased caloric use as a result of an heightened energy/metabolic state) 
 
=='''References''' ==
1) [http://www.science24.com/paper/6574 Science24.com/confernces] 
2) ''The effect of sibutramine-assisted weight loss in men with obstructive sleep apnoea'',International Journal of Obesity, 2 May 2006 
3) Malhotra A, White DP. Obstructive sleep apnoea. Lancet 2002; 360: 237–245 
4) Kim SH, Lee YM, Jee SH, Nam CM. Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 2003; 11: 1116–1123 
5) [http://www.myelectronicpharmacy.com My electronic pharmacy] 
6) [http://images.google.co.uk/imgres?imgurl=http://www.weightloss-news.com/graphics.htg/mermov.gif&imgrefurl=http://www.obesity-news.com/merfaq.htm&h=184&w=300&sz=40&hl=en&start=1&tbnid=ieLgEWX8ICsvJM:&tbnh=71&tbnw=116&prev=/images%3Fq%3Dsibutramine%26ndsp%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN Obesity Meds and Research News] 
7) http://www.rxlist.com/cgi/generic/sibutramine.htm 
8) http://www.chemsoc.org/ExemplarChem/entries/2003/imperial_Rowlands/index.html

It:Sibutramine

2006-10-30T12:13:27Z

Ylt05: added nmr

==Sibutramine==
{| class="toccolours" border="1" style="fix: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
|-
|align="center" colspan="3" bgcolor="white"|
[[Image:sibutramine.gif]]
|-
! {{chembox header}} colspan="3"| 3D structure
|-
| align="center" colspan="3" bgcolor="#ffffff" | <jmol>

<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 100; bns on;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>
HEADER Sibutramine NONE 1
TITLE NONE 2
AUTHOR WWW daemon apache NONE 3
REVDAT 1 20-Oct-06 0 NONE 4
ATOM 1 Cl 0 4.921 -0.468 -0.279 0.00 0.00 Cl+0
ATOM 2 C 0 3.242 -0.131 0.004 0.00 0.00 C+0
ATOM 3 C 0 2.815 0.248 1.264 0.00 0.00 C+0
ATOM 4 C 0 1.477 0.515 1.489 0.00 0.00 C+0
ATOM 5 C 0 0.567 0.404 0.455 0.00 0.00 C+0
ATOM 6 C 0 -0.891 0.695 0.700 0.00 0.00 C+0
ATOM 7 C 0 -1.777 0.347 -0.498 0.00 0.00 C+0
ATOM 8 N 0 -1.347 1.126 -1.667 0.00 0.00 N+0
ATOM 9 C 0 -1.872 0.433 -2.852 0.00 0.00 C+0
ATOM 10 C 0 -2.041 2.418 -1.591 0.00 0.00 C+0
ATOM 11 C 0 -1.653 -1.146 -0.807 0.00 0.00 C+0
ATOM 12 C 0 -2.199 -1.957 0.370 0.00 0.00 C+0
ATOM 13 C 0 -3.661 -1.577 0.617 0.00 0.00 C+0
ATOM 14 C 0 -2.108 -3.450 0.047 0.00 0.00 C+0
ATOM 15 C 0 -1.414 0.139 2.035 0.00 0.00 C+0
ATOM 16 C 0 -2.210 1.447 2.178 0.00 0.00 C+0
ATOM 17 C 0 -1.151 2.099 1.271 0.00 0.00 C+0
ATOM 18 C 0 0.993 0.025 -0.805 0.00 0.00 C+0
ATOM 19 C 0 2.331 -0.237 -1.032 0.00 0.00 C+0
ATOM 20 H 0 3.526 0.334 2.072 0.00 0.00 H+0
ATOM 21 H 0 1.144 0.811 2.472 0.00 0.00 H+0
ATOM 22 H 0 -2.814 0.585 -0.264 0.00 0.00 H+0
ATOM 23 H 0 -2.924 0.194 -2.696 0.00 0.00 H+0
ATOM 24 H 0 -1.771 1.079 -3.724 0.00 0.00 H+0
ATOM 25 H 0 -1.310 -0.486 -3.013 0.00 0.00 H+0
ATOM 26 H 0 -1.431 3.126 -1.030 0.00 0.00 H+0
ATOM 27 H 0 -2.207 2.801 -2.599 0.00 0.00 H+0
ATOM 28 H 0 -3.000 2.287 -1.090 0.00 0.00 H+0
ATOM 29 H 0 -2.225 -1.380 -1.705 0.00 0.00 H+0
ATOM 30 H 0 -0.605 -1.399 -0.967 0.00 0.00 H+0
ATOM 31 H 0 -1.612 -1.742 1.263 0.00 0.00 H+0
ATOM 32 H 0 -4.261 -1.862 -0.247 0.00 0.00 H+0
ATOM 33 H 0 -4.027 -2.098 1.502 0.00 0.00 H+0
ATOM 34 H 0 -3.735 -0.501 0.773 0.00 0.00 H+0
ATOM 35 H 0 -1.067 -3.721 -0.128 0.00 0.00 H+0
ATOM 36 H 0 -2.497 -4.028 0.886 0.00 0.00 H+0
ATOM 37 H 0 -2.695 -3.665 -0.845 0.00 0.00 H+0
ATOM 38 H 0 -2.043 -0.745 1.923 0.00 0.00 H+0
ATOM 39 H 0 -0.638 0.015 2.791 0.00 0.00 H+0
ATOM 40 H 0 -3.203 1.405 1.729 0.00 0.00 H+0
ATOM 41 H 0 -2.221 1.843 3.194 0.00 0.00 H+0
ATOM 42 H 0 -0.303 2.512 1.817 0.00 0.00 H+0
ATOM 43 H 0 -1.568 2.797 0.545 0.00 0.00 H+0
ATOM 44 H 0 0.281 -0.061 -1.612 0.00 0.00 H+0
ATOM 45 H 0 2.664 -0.533 -2.016 0.00 0.00 H+0
CONECT 1 2 0 0 0 NONE 50
CONECT 2 1 19 3 0 NONE 51
CONECT 3 2 4 20 0 NONE 52
CONECT 4 3 5 21 0 NONE 53
CONECT 5 4 6 18 0 NONE 54
CONECT 6 5 17 7 15 NONE 55
CONECT 7 6 8 11 22 NONE 56
CONECT 8 7 9 10 0 NONE 57
CONECT 9 8 23 24 25 NONE 58
CONECT 10 8 26 27 28 NONE 59
CONECT 11 7 12 29 30 NONE 60
CONECT 12 11 13 14 31 NONE 61
CONECT 13 12 32 33 34 NONE 62
CONECT 14 12 35 36 37 NONE 63
CONECT 15 6 16 38 39 NONE 64
CONECT 16 15 17 40 41 NONE 65
CONECT 17 16 6 42 43 NONE 66
CONECT 18 5 19 44 0 NONE 67
CONECT 19 18 2 45 0 NONE 68
END NONE 69
</inlineContents>
</jmolApplet>
</jmol>

|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2" | 1-(4-chlorophenyl)-N,N-dimethyl-α-(2-methylpropyl)-, hydrochloride, monohydrate
|-
| colspan="1" |Commercial names
| colspan="2" | MERIDIA (sibutramine hydrochloride monohydrate)
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" |C17H29Cl2NO
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |334.33
|-
| colspan="1" |Appearance
| colspan="2" |White to cream crystalline powder
|-
|colspan="1" |Beilstein Registry number
| colspan="2" |
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" |
|-
! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility] in [ http://en.wikipedia.org/wiki/Water_%28molecule%29 Water_(molecule)| Solubility in Water
| colspan="2" | 2.9 mg/mL in pH 5.2 water
|-
| Other solvents
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Melting_point Melting point]
| colspan="2" | 191-192°C
|-
| [http://en.wikipedia.org/wiki/Boiling_point Boiling point]
| colspan="2" |
|-
! {{chembox header}} colspan="3"| Structure
|-
| [http://en.wikipedia.org/wiki/Crystal_structure Crystal structure] 
| colspan="2"|
|-
| [http://en.wikipedia.org/wiki/Dipole#Molecular_dipoles Dipole moment]
| colspan="2" |
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| [http://en.wikipedia.org/wiki/Material_safety_data_sheet MSDS]
| colspan="2" |
|-
| 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" |
|-
| [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" | Spectral data
|-

| NMR
|align="center" colspan="3" bgcolor="white"|
[[Image:nmrsibutramine.gif]]
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|-
| {{chembox header}} colspan="3"| Except where noted otherwise, data are given for materials in their [http://en.wikipedia.org/wiki/Standard_state standard state (at 25 °C, 100 kPa)] [http://en.wikipedia.org/wiki/Wikipedia:Chemical_infobox Infobox disclaimer and references]]
|-
|}

 

=='''How is Sibutramine synthesized?'''==
[[Image:synthesissibu.gif|right|100|Reaction scheme showing Sibutramine synthesis]] 
The reaction scheme shown on the right gives an overview of how Sibutramine is synthesized1. Known methods for preparation of crucial intermediate in the synthesis of ''1-1-(4-chlorophenyl)-1-cyanocyclobutane'' consist of cycloalkylation of 4-chlorophenylacetonitrile with 1,3-dibromopropane in the presence of such base/solvent systems as: NaH/DMSO/ether, solid KOH/DMSO/ether, solid KOH/toluene/quaternary ammonium salt as a catalyst (solid - liquid phase transfer catalysis, PTC). All of them are inconvenient for large scale applications. On the other hand, it is now commonly accepted, that liquid-liquid PTC (conc. aq. solution of NaOH as a base) is the best practical procedure for alkylation of carbanions of arylacetonitriles and their derivatives. However, with 1,3-dibromopropane under typical PTC conditions (50% NaOH aq. as a base) yields of 1-aryl-1-cyanocyclobutanes are low, b-elimination of HBr from the alkylating agent is often observed, leading to mono- and diallylated arylacetonitriles as by product, which are difficult to separate.

It was experimentally observed that a simple change of 50% NaOH for 60% KOH overcomes all the difficulties mentioned above. Cycloalkylation of 4-chlorophenylacetonitrile with 1,3-dibromopropane carried out in the presence of 60% KOH and tetrabutylammonium bromide (TBAB) as a catalyst in toluene as a solvent proceeds in high yield, b-elimination of HBr from the alkylating agent practically does not proceed and isolation of ''1-1-(4-chlorophenyl)-1-cyanocyclobutane'' is pretty simple. This process was performed on a 10 mol scale, with the yields exceeding 70%.
 
 
 
 
 
== '''How does Sibutramine aid in weight loss?''' ==
Sibutramine pills5: 
[[Image:sibutramine.jpg|60|Sibutramine pills]] 
Sibutramine primarily works by increasing feelings of satiety and reducing appetite. It is recommended to patients with a BMI of 30kg m-2 or more for aiding weight loss by reducing appetite and increasing satiety. 
It increases blood pressure in some patients4 and therefore blood pressure must be monitored during treatment to ensure that it does not become dangerously high. 
However, the weight loss as a result of using Sibutramine does not come without a price. Side effects of Sibutramine include dry mouth, constipation and insomnia. Less common side effects include headache, increased sweating, increased blood pressure and increased heart rate. Of these, the issue of increased blood pressure is the most concerning, but it is less common and since patients with obesity are regularly monitored by their doctors for changes in blood pressure, this risk is mitigated somewhat2. In addition, Sibutramine should not be prescribed for people with a history of coronary artery disease, congestive heart failure, arrhythmias or stroke, as it may dangerously increase the individual's heart rate and/or blood pressure. 
 
=='''Working principles behind Sibutramine''' ==
[[Image:neuro.gif|right|100|Working principle behind Sibutramine]]
Sibutramine (commercially known as Meridia®) is an equipotent serotonin and norepinephrine reuptake inhibitor (SNRI), which means it has an equal effect on serotonin (a brain neurotransmitter which generally promotes a calming feeling) and norepinephrine (a stimulant). The diagram on the right shows how this is brought about6. Research indicates that these brain chemicals have an effect on appetite and satiety. 

Animals given sibutramine have shown an increase in metabolic rate3, but human studies have not been conclusive. The reasons for the difference between animals and humans is not clear but may be due to the small number of subjects tested and the small effect of the drug on energy expenditure. However, even small increases in thermogenesis could be clinically significant in weight loss and weight maintenance. (Thermogenesis refers to increased fat loss through raising the body's core temperature or through an increased caloric use as a result of an heightened energy/metabolic state) 
 
=='''References''' ==
1) [http://www.science24.com/paper/6574 Science24.com/confernces] 
2) ''The effect of sibutramine-assisted weight loss in men with obstructive sleep apnoea'',International Journal of Obesity, 2 May 2006 
3) Malhotra A, White DP. Obstructive sleep apnoea. Lancet 2002; 360: 237–245 
4) Kim SH, Lee YM, Jee SH, Nam CM. Effect of sibutramine on weight loss and blood pressure: a meta-analysis of controlled trials. Obes Res 2003; 11: 1116–1123 
5) [http://www.myelectronicpharmacy.com My electronic pharmacy] 
6) [http://images.google.co.uk/imgres?imgurl=http://www.weightloss-news.com/graphics.htg/mermov.gif&imgrefurl=http://www.obesity-news.com/merfaq.htm&h=184&w=300&sz=40&hl=en&start=1&tbnid=ieLgEWX8ICsvJM:&tbnh=71&tbnw=116&prev=/images%3Fq%3Dsibutramine%26ndsp%3D20%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DN Obesity Meds and Research News] 
7) http://www.rxlist.com/cgi/generic/sibutramine.htm 
8) http://www.chemsoc.org/ExemplarChem/entries/2003/imperial_Rowlands/index.html

2006-10-24T13:45:07Z

Ylt05:

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Substructure of Capreomycin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:Capreomycin.gif|200px|{{PAGENAME}}]]
|-
! {{chembox header}} colspan="3" | Possible R groups
|-
| colspan="1" |'''Analogue'''
| colspan="1" |'''R1'''
| colspan="1" |'''R2'''
|-
| colspan="1" |Capreomycin IA|| colspan="1" | OH || colspan="1" | β-Lys
|-
| colspan="1" |Capreomycin IB|| colspan="1" | H || colspan="1" |β-Lys
|-
| colspan="1" |Capreomycin IIA|| colspan="1" | OH || colspan="1" | NH2
|-
| colspan="1" |Capreomycin IIB|| colspan="1" | H || colspan="1" | NH2
|-
! {{chembox header}} colspan="3" |3D structure
|-
| align="center" colspan="3" bgcolor="#ffffff" | <jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 100; cpk off;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>HEADER CSD ENTRY XICKAV
CRYST1 8.5594 6.0337 11.0220 90.00 105.97 90.00 P21/c
SCALE1 0.116831 -0.000000 0.033428 0.000000
SCALE2 -0.000000 0.165736 -0.000000 0.000000
SCALE3 -0.000000 0.000000 0.094368 0.000000

ATOM 1 N 0 9.635 0.272 1.431 0.00 0.00 N+0

ATOM 2 C 0 8.738 0.894 0.719 0.00 0.00 C+0

ATOM 3 N 0 8.904 2.212 0.324 0.00 0.00 N+0

ATOM 4 C 0 7.736 3.102 0.425 0.00 0.00 C+0

ATOM 5 C 0 6.537 2.414 -0.237 0.00 0.00 C+0

ATOM 6 C 0 6.318 1.045 0.416 0.00 0.00 C+0

ATOM 7 C 0 5.194 0.303 -0.309 0.00 0.00 C+0

ATOM 8 C 0 4.977 -1.046 0.331 0.00 0.00 C+0

ATOM 9 N 0 4.240 -1.977 -0.351 0.00 0.00 N+0

ATOM 10 C 0 4.005 -3.241 0.391 0.00 0.00 C+0

ATOM 11 C 0 2.830 -3.973 -0.261 0.00 0.00 C+0

ATOM 12 C 0 1.532 -3.357 0.196 0.00 0.00 C+0

ATOM 13 N 0 0.356 -3.942 -0.195 0.00 0.00 N+0

ATOM 14 C 0 -0.864 -3.279 0.329 0.00 0.00 C+0

ATOM 15 C 0 -1.061 -1.985 -0.418 0.00 0.00 C+0

ATOM 16 N 0 -1.996 -1.100 0.026 0.00 0.00 N+0

ATOM 17 C 0 -2.119 0.158 -0.745 0.00 0.00 C+0

ATOM 18 C 0 -3.314 0.964 -0.232 0.00 0.00 C+0

ATOM 19 N 0 -4.539 0.176 -0.390 0.00 0.00 N+0

ATOM 20 C 0 -5.724 0.688 -0.003 0.00 0.00 C+0

ATOM 21 C 0 -6.984 -0.122 -0.166 0.00 0.00 C+0

ATOM 22 C 0 -8.179 0.684 0.347 0.00 0.00 C+0

ATOM 23 N 0 -8.296 1.930 -0.421 0.00 0.00 N+0

ATOM 24 C 0 -9.458 -0.139 0.182 0.00 0.00 C+0

ATOM 25 C 0 -10.653 0.667 0.695 0.00 0.00 C+0

ATOM 26 C 0 -11.932 -0.156 0.530 0.00 0.00 C+0

ATOM 27 N 0 -13.080 0.618 1.023 0.00 0.00 N+0

ATOM 28 O 0 -5.777 1.801 0.477 0.00 0.00 O+0

ATOM 29 C 0 -0.847 0.952 -0.552 0.00 0.00 C+0

ATOM 30 N 0 0.339 0.319 -0.813 0.00 0.00 N+0

ATOM 31 O 0 -0.875 2.106 -0.181 0.00 0.00 O+0

ATOM 32 O 0 -0.396 -1.736 -1.401 0.00 0.00 O+0

ATOM 33 C 0 -2.076 -4.187 0.113 0.00 0.00 C+0

ATOM 34 O 0 -1.874 -5.422 0.803 0.00 0.00 O+0

ATOM 35 O 0 1.529 -2.365 0.894 0.00 0.00 O+0

ATOM 36 N 0 2.936 -3.864 -1.722 0.00 0.00 N+0

ATOM 37 O 0 5.443 -1.299 1.422 0.00 0.00 O+0

ATOM 38 N 0 3.935 1.072 -0.199 0.00 0.00 N+0

ATOM 39 C 0 2.805 0.417 -0.585 0.00 0.00 C+0

ATOM 40 C 0 1.503 1.067 -0.452 0.00 0.00 C+0

ATOM 41 C 0 1.402 2.335 -0.002 0.00 0.00 C+0

ATOM 42 N 0 0.611 3.243 -0.671 0.00 0.00 N+0

ATOM 43 C 0 0.411 4.472 -0.155 0.00 0.00 C+0

ATOM 44 N 0 -0.362 5.360 -0.811 0.00 0.00 N+0

ATOM 45 O 0 0.928 4.779 0.901 0.00 0.00 O+0

ATOM 46 O 0 2.880 -0.709 -1.042 0.00 0.00 O+0

ATOM 47 N 0 7.569 0.269 0.311 0.00 0.00 N+0

ATOM 48 H 0 10.446 0.733 1.699 0.00 0.00 H+0

ATOM 49 H 0 9.757 2.536 -0.006 0.00 0.00 H+0

ATOM 50 H 0 7.514 3.296 1.474 0.00 0.00 H+0

ATOM 51 H 0 7.947 4.042 -0.087 0.00 0.00 H+0

ATOM 52 H 0 5.646 3.027 -0.104 0.00 0.00 H+0

ATOM 53 H 0 6.733 2.283 -1.301 0.00 0.00 H+0

ATOM 54 H 0 6.051 1.178 1.465 0.00 0.00 H+0

ATOM 55 H 0 5.457 0.173 -1.359 0.00 0.00 H+0

ATOM 56 H 0 3.900 -1.823 -1.246 0.00 0.00 H+0

ATOM 57 H 0 4.897 -3.865 0.345 0.00 0.00 H+0

ATOM 58 H 0 3.765 -3.016 1.431 0.00 0.00 H+0

ATOM 59 H 0 2.854 -5.025 0.027 0.00 0.00 H+0

ATOM 60 H 0 0.324 -4.725 -0.766 0.00 0.00 H+0

ATOM 61 H 0 -0.741 -3.073 1.392 0.00 0.00 H+0

ATOM 62 H 0 -2.549 -1.282 0.801 0.00 0.00 H+0

ATOM 63 H 0 -2.256 -0.070 -1.802 0.00 0.00 H+0

ATOM 64 H 0 -3.167 1.200 0.823 0.00 0.00 H+0

ATOM 65 H 0 -3.401 1.889 -0.802 0.00 0.00 H+0

ATOM 66 H 0 -4.497 -0.714 -0.774 0.00 0.00 H+0

ATOM 67 H 0 -7.131 -0.358 -1.220 0.00 0.00 H+0

ATOM 68 H 0 -6.898 -1.047 0.404 0.00 0.00 H+0

ATOM 69 H 0 -8.032 0.919 1.402 0.00 0.00 H+0

ATOM 70 H 0 -8.429 1.665 -1.386 0.00 0.00 H+0

ATOM 71 H 0 -9.150 2.376 -0.122 0.00 0.00 H+0

ATOM 72 H 0 -9.605 -0.375 -0.872 0.00 0.00 H+0

ATOM 73 H 0 -9.372 -1.064 0.752 0.00 0.00 H+0

ATOM 74 H 0 -10.507 0.903 1.749 0.00 0.00 H+0

ATOM 75 H 0 -10.740 1.592 0.125 0.00 0.00 H+0

ATOM 76 H 0 -12.079 -0.391 -0.524 0.00 0.00 H+0

ATOM 77 H 0 -11.846 -1.081 1.100 0.00 0.00 H+0

ATOM 78 H 0 -13.896 0.040 0.894 0.00 0.00 H+0

ATOM 79 H 0 -12.952 0.723 2.018 0.00 0.00 H+0

ATOM 80 H 0 0.386 -0.565 -1.210 0.00 0.00 H+0

ATOM 81 H 0 -2.970 -3.697 0.498 0.00 0.00 H+0

ATOM 82 H 0 -2.198 -4.382 -0.953 0.00 0.00 H+0

ATOM 83 H 0 -2.659 -5.964 0.641 0.00 0.00 H+0

ATOM 84 H 0 2.146 -4.359 -2.107 0.00 0.00 H+0

ATOM 85 H 0 2.808 -2.890 -1.950 0.00 0.00 H+0

ATOM 86 H 0 3.915 1.985 0.128 0.00 0.00 H+0

ATOM 87 H 0 1.940 2.638 0.884 0.00 0.00 H+0

ATOM 88 H 0 0.198 2.998 -1.514 0.00 0.00 H+0

ATOM 89 H 0 -0.506 6.245 -0.439 0.00 0.00 H+0

ATOM 90 H 0 -0.775 5.115 -1.653 0.00 0.00 H+0

ATOM 91 H 0 7.571 -0.641 -0.025 0.00 0.00 H+0

CONECT 1 2 48 0 0 NONE 96

CONECT 2 1 47 3 0 NONE 97

CONECT 3 2 4 49 0 NONE 98

CONECT 4 3 5 50 51 NONE 99

CONECT 5 4 6 52 53 NONE 100

CONECT 6 5 7 47 54 NONE 101

CONECT 7 6 8 38 55 NONE 102

CONECT 8 7 9 37 0 NONE 103

CONECT 9 8 10 56 0 NONE 104

CONECT 10 9 11 57 58 NONE 105

CONECT 11 10 12 36 59 NONE 106

CONECT 12 11 13 35 0 NONE 107

CONECT 13 12 14 60 0 NONE 108

CONECT 14 13 15 33 61 NONE 109

CONECT 15 14 16 32 0 NONE 110

CONECT 16 15 17 62 0 NONE 111

CONECT 17 16 18 29 63 NONE 112

CONECT 18 17 19 64 65 NONE 113

CONECT 19 18 20 66 0 NONE 114

CONECT 20 19 21 28 0 NONE 115

CONECT 21 20 22 67 68 NONE 116

CONECT 22 21 23 24 69 NONE 117

CONECT 23 22 70 71 0 NONE 118

CONECT 24 22 25 72 73 NONE 119

CONECT 25 24 26 74 75 NONE 120

CONECT 26 25 27 76 77 NONE 121

CONECT 27 26 78 79 0 NONE 122

CONECT 28 20 0 0 0 NONE 123

CONECT 29 17 30 31 0 NONE 124

CONECT 30 29 40 80 0 NONE 125

CONECT 31 29 0 0 0 NONE 126

CONECT 32 15 0 0 0 NONE 127

CONECT 33 14 34 81 82 NONE 128

CONECT 34 33 83 0 0 NONE 129

CONECT 35 12 0 0 0 NONE 130

CONECT 36 11 84 85 0 NONE 131

CONECT 37 8 0 0 0 NONE 132

CONECT 38 7 39 86 0 NONE 133

CONECT 39 38 40 46 0 NONE 134

CONECT 40 39 30 41 0 NONE 135

CONECT 41 40 42 87 0 NONE 136

CONECT 42 41 43 88 0 NONE 137

CONECT 43 42 44 45 0 NONE 138

CONECT 44 43 89 90 0 NONE 139

CONECT 45 43 0 0 0 NONE 140

CONECT 46 39 0 0 0 NONE 141

CONECT 47 6 2 91 0 NONE 142

NONE 143
END</inlineContents>
</jmolApplet>
</jmol>
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|
|-
| colspan="1" |Auto name
| colspan="2" |
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" | C25H43N13O8
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |?
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |653.70 g/mol
|-
| colspan="1" |Appearance
| colspan="2" |
|-
|colspan="1" |Beilstein Registry number
| colspan="2" | 876587
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" | 61394-77-2
|-
! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Density Density] and [http://en.wikipedia.org/wiki/Phase_%28matter%29 Phase (matter)|phase]
| colspan="2" | g/cm
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility] in [ http://en.wikipedia.org/wiki/Water_%28molecule%29 Water_(molecule)|water]
| colspan="2" |
|-
| Other solvents
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Melting_point Melting point]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Boiling_point Boiling point]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K'') 
| colspan="2" |?
|-
! {{chembox header}} colspan="3"| Structure
|-
| [http://en.wikipedia.org/wiki/Crystal_structure Crystal structure] 
| colspan="2"|
|-
| [http://en.wikipedia.org/wiki/Dipole#Molecular_dipoles Dipole moment]
| colspan="2" |? [http://en.wikipedia.org/wiki/Debye D]
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| [http://en.wikipedia.org/wiki/Material_safety_data_sheet MSDS]
| colspan="2" |[[{{PAGENAME}} (data page)#Material Safety Data Sheet|External MSDS]] 
|-
| 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" |
|-
| [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" | [[{{PAGENAME}} (data page)|Supplementary data page]]
|-
| Structure and properties
| colspan="2" |
|-
| Thermodynamic data
| colspan="2" |
|-
| Spectral data
| colspan="2" | [[UV/VIS spectroscopy|UV]], [[Infrared spectroscopy|IR]], [[nuclear magnetic resonance spectroscopy|NMR]], [[Mass spectrometry|MS]]
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|-
| {{chembox header}} colspan="3"| Except where noted otherwise, data are given for materials in their [http://en.wikipedia.org/wiki/Standard_state standard state (at 25 °C, 100 kPa)] [http://en.wikipedia.org/wiki/Wikipedia:Chemical_infobox Infobox disclaimer and references]]
|-
|}

'''Capreomycin''' is an antibiotic in the family of [http://en.wikipedia.org/wiki/Aminoglycosides aminoglycosides]. Capreomycin is effective against a number of [http://en.wikipedia.org/wiki/Gram_positive Gram-positive] and [http://en.wikipedia.org/wiki/Gram-negative Gram-negative] bacteria, and finds particular application against [http://en.wikipedia.org/wiki/Mycobacterium mycobacteria] such as [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] which causes [http://en.wikipedia.org/wiki/Tuberculosis tuberculosis].

Capreomycins have been particularly successful in treating the various strains of the bacterium ''Mycobacterium tuberculosis'', and hence are extremely valuable to patients who do not respond to drugs commonly used to treat TB. Capreomycin is normally prescribed together with other medications, preventing the patient from developing sole resistance to the drug. Capreomycin is injected into the patient, as it cannot be absorbed through the digestive tract. It causes the malfunction of the protein production of the bacteria, effectively eliminating the bacteria from the patient’s body.[http://www.netdoctor.co.uk/medicines/100000447.html]

==Synthesis==

In 1959, the tuberculostatic cyclic peptide antibiotics capreomycins IA, IB, IIA, and IIB were isolated from ''Streptomyces capreolus'' by Herr and co-workers at Eli Lilly.[2] Shiba and co-workers then completed the syntheses of capreomycins IA and IB.[3] The synthesis of capreomycin IB has been simplified to a 27-step synthesis route proposed by DeMong and Williams.[4]

'''Structures of the capreomycins'''

[[Image:Capreomycin0.gif]]

'''Scheme 1: Enolate-Aldimine Reaction'''

The asymmetric (2''S'',3''R'')-capreomycidine '''2''' was synthesised via an enolate-aldimine condensation between chiral glycinate (-)-'''5''' and benzyl imine '''4'''.

[[Image:Capreomycin1.gif]]

'''Scheme 2 and 3: Completion of (2''S'',3''R'')-Capreomycidine and Preparation of R-α-Formylglycine Dimethylacetal '''

DeMong and Williams adapted titanium enolate chemistry to prepare an enantiomerically pure form of α-formylglycine dimethylacetal '''11'''. Triethylorthoformate was added to the titanium enolate of (+)-'''5''' to provide an 85% yield of diethylacetal '''10'''. Hydrogenolysis of '''10''' provided clean conversion to R-α-formylglycine diethylacetal '''11'''.

[[Image:Capreomycin2.gif]]

[[Image:Capreomycin3.gif]]

'''Scheme 4 and 5: Preparation of DAPA-β-lysine Dipeptide and Tripeptide Formation'''

The protected diaminopropanoic acid-β-lysine dipeptide '''13''' was prepared from an oxidative Hofmann rearrangement of N-CBz-asparagine. The methyl ester in '''15''' was hydrolysed to give a quantitative yield of carboxylic acid '''16'''.

[[Image:Capreomycin4.gif]]

[[Image:Capreomycin5.gif]]

'''Scheme 6 and 7: Pentapeptide Formation and Completion of Capreomycin IB'''

[[Image:Capreomycin6.gif]]

[[Image:Capreomycin7.gif]]

==Properties and structure==

==Uses==

==References==

1. http://www.netdoctor.co.uk/medicines/100000447.html

2. Herr, E. B.; Haney, M. E.; Pittenger, G. E.; Higgens, C. E. Proc. Ind. Acad. Sci. 1960, 69, 134.

3. (a) Shiba, T.; Nomoto, S.; Teshima, T.; Wakamiya, T. Tetrahedron Lett. 1976, 17, 3907-3910. (b) Nomoto, S.; Teshima, T.; Wakamiya, T.; Shiba, T. J. Antibiot. 1977, 30, 955-959. (c) Nomoto, S.; Teshima, T.; Wakamiya, T.; Shiba, T. Tetrahedron 1978, 34, 921-927.

4. DeMong, D. E.; Williams, R. M.; J. Am. Chem. Soc., 125 (28), 8561-8565, 2003.

File:Capreomycin7.gif

2006-10-24T13:43:56Z

Ylt05:

2006-10-24T13:22:56Z

Ylt05:

2006-10-24T13:04:27Z

Ylt05:

It:Capreomycin

2006-10-24T13:04:19Z

Ylt05:

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Substructure of Capreomycin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:Capreomycin.gif|200px|{{PAGENAME}}]]
|-
! {{chembox header}} colspan="3" | Possible R groups
|-
| colspan="1" |'''Analogue'''
| colspan="1" |'''R1'''
| colspan="1" |'''R2'''
|-
| colspan="1" |Capreomycin IA|| colspan="1" | OH || colspan="1" | β-Lys
|-
| colspan="1" |Capreomycin IB|| colspan="1" | H || colspan="1" |β-Lys
|-
| colspan="1" |Capreomycin IIA|| colspan="1" | OH || colspan="1" | NH2
|-
| colspan="1" |Capreomycin IIB|| colspan="1" | H || colspan="1" | NH2
|-
! {{chembox header}} colspan="3" |3D structure
|-
| align="center" colspan="3" bgcolor="#ffffff" | <jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 100; cpk off;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>HEADER CSD ENTRY XICKAV
CRYST1 8.5594 6.0337 11.0220 90.00 105.97 90.00 P21/c
SCALE1 0.116831 -0.000000 0.033428 0.000000
SCALE2 -0.000000 0.165736 -0.000000 0.000000
SCALE3 -0.000000 0.000000 0.094368 0.000000

ATOM 1 N 0 9.635 0.272 1.431 0.00 0.00 N+0

ATOM 2 C 0 8.738 0.894 0.719 0.00 0.00 C+0

ATOM 3 N 0 8.904 2.212 0.324 0.00 0.00 N+0

ATOM 4 C 0 7.736 3.102 0.425 0.00 0.00 C+0

ATOM 5 C 0 6.537 2.414 -0.237 0.00 0.00 C+0

ATOM 6 C 0 6.318 1.045 0.416 0.00 0.00 C+0

ATOM 7 C 0 5.194 0.303 -0.309 0.00 0.00 C+0

ATOM 8 C 0 4.977 -1.046 0.331 0.00 0.00 C+0

ATOM 9 N 0 4.240 -1.977 -0.351 0.00 0.00 N+0

ATOM 10 C 0 4.005 -3.241 0.391 0.00 0.00 C+0

ATOM 11 C 0 2.830 -3.973 -0.261 0.00 0.00 C+0

ATOM 12 C 0 1.532 -3.357 0.196 0.00 0.00 C+0

ATOM 13 N 0 0.356 -3.942 -0.195 0.00 0.00 N+0

ATOM 14 C 0 -0.864 -3.279 0.329 0.00 0.00 C+0

ATOM 15 C 0 -1.061 -1.985 -0.418 0.00 0.00 C+0

ATOM 16 N 0 -1.996 -1.100 0.026 0.00 0.00 N+0

ATOM 17 C 0 -2.119 0.158 -0.745 0.00 0.00 C+0

ATOM 18 C 0 -3.314 0.964 -0.232 0.00 0.00 C+0

ATOM 19 N 0 -4.539 0.176 -0.390 0.00 0.00 N+0

ATOM 20 C 0 -5.724 0.688 -0.003 0.00 0.00 C+0

ATOM 21 C 0 -6.984 -0.122 -0.166 0.00 0.00 C+0

ATOM 22 C 0 -8.179 0.684 0.347 0.00 0.00 C+0

ATOM 23 N 0 -8.296 1.930 -0.421 0.00 0.00 N+0

ATOM 24 C 0 -9.458 -0.139 0.182 0.00 0.00 C+0

ATOM 25 C 0 -10.653 0.667 0.695 0.00 0.00 C+0

ATOM 26 C 0 -11.932 -0.156 0.530 0.00 0.00 C+0

ATOM 27 N 0 -13.080 0.618 1.023 0.00 0.00 N+0

ATOM 28 O 0 -5.777 1.801 0.477 0.00 0.00 O+0

ATOM 29 C 0 -0.847 0.952 -0.552 0.00 0.00 C+0

ATOM 30 N 0 0.339 0.319 -0.813 0.00 0.00 N+0

ATOM 31 O 0 -0.875 2.106 -0.181 0.00 0.00 O+0

ATOM 32 O 0 -0.396 -1.736 -1.401 0.00 0.00 O+0

ATOM 33 C 0 -2.076 -4.187 0.113 0.00 0.00 C+0

ATOM 34 O 0 -1.874 -5.422 0.803 0.00 0.00 O+0

ATOM 35 O 0 1.529 -2.365 0.894 0.00 0.00 O+0

ATOM 36 N 0 2.936 -3.864 -1.722 0.00 0.00 N+0

ATOM 37 O 0 5.443 -1.299 1.422 0.00 0.00 O+0

ATOM 38 N 0 3.935 1.072 -0.199 0.00 0.00 N+0

ATOM 39 C 0 2.805 0.417 -0.585 0.00 0.00 C+0

ATOM 40 C 0 1.503 1.067 -0.452 0.00 0.00 C+0

ATOM 41 C 0 1.402 2.335 -0.002 0.00 0.00 C+0

ATOM 42 N 0 0.611 3.243 -0.671 0.00 0.00 N+0

ATOM 43 C 0 0.411 4.472 -0.155 0.00 0.00 C+0

ATOM 44 N 0 -0.362 5.360 -0.811 0.00 0.00 N+0

ATOM 45 O 0 0.928 4.779 0.901 0.00 0.00 O+0

ATOM 46 O 0 2.880 -0.709 -1.042 0.00 0.00 O+0

ATOM 47 N 0 7.569 0.269 0.311 0.00 0.00 N+0

ATOM 48 H 0 10.446 0.733 1.699 0.00 0.00 H+0

ATOM 49 H 0 9.757 2.536 -0.006 0.00 0.00 H+0

ATOM 50 H 0 7.514 3.296 1.474 0.00 0.00 H+0

ATOM 51 H 0 7.947 4.042 -0.087 0.00 0.00 H+0

ATOM 52 H 0 5.646 3.027 -0.104 0.00 0.00 H+0

ATOM 53 H 0 6.733 2.283 -1.301 0.00 0.00 H+0

ATOM 54 H 0 6.051 1.178 1.465 0.00 0.00 H+0

ATOM 55 H 0 5.457 0.173 -1.359 0.00 0.00 H+0

ATOM 56 H 0 3.900 -1.823 -1.246 0.00 0.00 H+0

ATOM 57 H 0 4.897 -3.865 0.345 0.00 0.00 H+0

ATOM 58 H 0 3.765 -3.016 1.431 0.00 0.00 H+0

ATOM 59 H 0 2.854 -5.025 0.027 0.00 0.00 H+0

ATOM 60 H 0 0.324 -4.725 -0.766 0.00 0.00 H+0

ATOM 61 H 0 -0.741 -3.073 1.392 0.00 0.00 H+0

ATOM 62 H 0 -2.549 -1.282 0.801 0.00 0.00 H+0

ATOM 63 H 0 -2.256 -0.070 -1.802 0.00 0.00 H+0

ATOM 64 H 0 -3.167 1.200 0.823 0.00 0.00 H+0

ATOM 65 H 0 -3.401 1.889 -0.802 0.00 0.00 H+0

ATOM 66 H 0 -4.497 -0.714 -0.774 0.00 0.00 H+0

ATOM 67 H 0 -7.131 -0.358 -1.220 0.00 0.00 H+0

ATOM 68 H 0 -6.898 -1.047 0.404 0.00 0.00 H+0

ATOM 69 H 0 -8.032 0.919 1.402 0.00 0.00 H+0

ATOM 70 H 0 -8.429 1.665 -1.386 0.00 0.00 H+0

ATOM 71 H 0 -9.150 2.376 -0.122 0.00 0.00 H+0

ATOM 72 H 0 -9.605 -0.375 -0.872 0.00 0.00 H+0

ATOM 73 H 0 -9.372 -1.064 0.752 0.00 0.00 H+0

ATOM 74 H 0 -10.507 0.903 1.749 0.00 0.00 H+0

ATOM 75 H 0 -10.740 1.592 0.125 0.00 0.00 H+0

ATOM 76 H 0 -12.079 -0.391 -0.524 0.00 0.00 H+0

ATOM 77 H 0 -11.846 -1.081 1.100 0.00 0.00 H+0

ATOM 78 H 0 -13.896 0.040 0.894 0.00 0.00 H+0

ATOM 79 H 0 -12.952 0.723 2.018 0.00 0.00 H+0

ATOM 80 H 0 0.386 -0.565 -1.210 0.00 0.00 H+0

ATOM 81 H 0 -2.970 -3.697 0.498 0.00 0.00 H+0

ATOM 82 H 0 -2.198 -4.382 -0.953 0.00 0.00 H+0

ATOM 83 H 0 -2.659 -5.964 0.641 0.00 0.00 H+0

ATOM 84 H 0 2.146 -4.359 -2.107 0.00 0.00 H+0

ATOM 85 H 0 2.808 -2.890 -1.950 0.00 0.00 H+0

ATOM 86 H 0 3.915 1.985 0.128 0.00 0.00 H+0

ATOM 87 H 0 1.940 2.638 0.884 0.00 0.00 H+0

ATOM 88 H 0 0.198 2.998 -1.514 0.00 0.00 H+0

ATOM 89 H 0 -0.506 6.245 -0.439 0.00 0.00 H+0

ATOM 90 H 0 -0.775 5.115 -1.653 0.00 0.00 H+0

ATOM 91 H 0 7.571 -0.641 -0.025 0.00 0.00 H+0

CONECT 1 2 48 0 0 NONE 96

CONECT 2 1 47 3 0 NONE 97

CONECT 3 2 4 49 0 NONE 98

CONECT 4 3 5 50 51 NONE 99

CONECT 5 4 6 52 53 NONE 100

CONECT 6 5 7 47 54 NONE 101

CONECT 7 6 8 38 55 NONE 102

CONECT 8 7 9 37 0 NONE 103

CONECT 9 8 10 56 0 NONE 104

CONECT 10 9 11 57 58 NONE 105

CONECT 11 10 12 36 59 NONE 106

CONECT 12 11 13 35 0 NONE 107

CONECT 13 12 14 60 0 NONE 108

CONECT 14 13 15 33 61 NONE 109

CONECT 15 14 16 32 0 NONE 110

CONECT 16 15 17 62 0 NONE 111

CONECT 17 16 18 29 63 NONE 112

CONECT 18 17 19 64 65 NONE 113

CONECT 19 18 20 66 0 NONE 114

CONECT 20 19 21 28 0 NONE 115

CONECT 21 20 22 67 68 NONE 116

CONECT 22 21 23 24 69 NONE 117

CONECT 23 22 70 71 0 NONE 118

CONECT 24 22 25 72 73 NONE 119

CONECT 25 24 26 74 75 NONE 120

CONECT 26 25 27 76 77 NONE 121

CONECT 27 26 78 79 0 NONE 122

CONECT 28 20 0 0 0 NONE 123

CONECT 29 17 30 31 0 NONE 124

CONECT 30 29 40 80 0 NONE 125

CONECT 31 29 0 0 0 NONE 126

CONECT 32 15 0 0 0 NONE 127

CONECT 33 14 34 81 82 NONE 128

CONECT 34 33 83 0 0 NONE 129

CONECT 35 12 0 0 0 NONE 130

CONECT 36 11 84 85 0 NONE 131

CONECT 37 8 0 0 0 NONE 132

CONECT 38 7 39 86 0 NONE 133

CONECT 39 38 40 46 0 NONE 134

CONECT 40 39 30 41 0 NONE 135

CONECT 41 40 42 87 0 NONE 136

CONECT 42 41 43 88 0 NONE 137

CONECT 43 42 44 45 0 NONE 138

CONECT 44 43 89 90 0 NONE 139

CONECT 45 43 0 0 0 NONE 140

CONECT 46 39 0 0 0 NONE 141

CONECT 47 6 2 91 0 NONE 142

NONE 143
END</inlineContents>
</jmolApplet>
</jmol>
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|
|-
| colspan="1" |Auto name
| colspan="2" |
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" | C25H43N13O8
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |?
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |653.70 g/mol
|-
| colspan="1" |Appearance
| colspan="2" |
|-
|colspan="1" |Beilstein Registry number
| colspan="2" | 876587
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" | 61394-77-2
|-
! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Density Density] and [http://en.wikipedia.org/wiki/Phase_%28matter%29 Phase (matter)|phase]
| colspan="2" | g/cm
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility] in [ http://en.wikipedia.org/wiki/Water_%28molecule%29 Water_(molecule)|water]
| colspan="2" |
|-
| Other solvents
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Melting_point Melting point]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Boiling_point Boiling point]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K'') 
| colspan="2" |?
|-
! {{chembox header}} colspan="3"| Structure
|-
| [http://en.wikipedia.org/wiki/Crystal_structure Crystal structure] 
| colspan="2"|
|-
| [http://en.wikipedia.org/wiki/Dipole#Molecular_dipoles Dipole moment]
| colspan="2" |? [http://en.wikipedia.org/wiki/Debye D]
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| [http://en.wikipedia.org/wiki/Material_safety_data_sheet MSDS]
| colspan="2" |[[{{PAGENAME}} (data page)#Material Safety Data Sheet|External MSDS]] 
|-
| 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" |
|-
| [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" | [[{{PAGENAME}} (data page)|Supplementary data page]]
|-
| Structure and properties
| colspan="2" |
|-
| Thermodynamic data
| colspan="2" |
|-
| Spectral data
| colspan="2" | [[UV/VIS spectroscopy|UV]], [[Infrared spectroscopy|IR]], [[nuclear magnetic resonance spectroscopy|NMR]], [[Mass spectrometry|MS]]
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|-
| {{chembox header}} colspan="3"| Except where noted otherwise, data are given for materials in their [http://en.wikipedia.org/wiki/Standard_state standard state (at 25 °C, 100 kPa)] [http://en.wikipedia.org/wiki/Wikipedia:Chemical_infobox Infobox disclaimer and references]]
|-
|}

'''Capreomycin''' is an antibiotic in the family of [http://en.wikipedia.org/wiki/Aminoglycosides aminoglycosides]. Capreomycin is effective against a number of [http://en.wikipedia.org/wiki/Gram_positive Gram-positive] and [http://en.wikipedia.org/wiki/Gram-negative Gram-negative] bacteria, and finds particular application against [http://en.wikipedia.org/wiki/Mycobacterium mycobacteria] such as [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] which causes [http://en.wikipedia.org/wiki/Tuberculosis tuberculosis].

Capreomycins have been particularly successful in treating the various strains of the bacterium ''Mycobacterium tuberculosis'', and hence are extremely valuable to patients who do not respond to drugs commonly used to treat TB. Capreomycin is normally prescribed together with other medications, preventing the patient from developing sole resistance to the drug. Capreomycin is injected into the patient, as it cannot be absorbed through the digestive tract. It causes the malfunction of the protein production of the bacteria, effectively eliminating the bacteria from the patient’s body.[http://www.netdoctor.co.uk/medicines/100000447.html]

==Synthesis==

In 1959, the tuberculostatic cyclic peptide antibiotics capreomycins IA, IB, IIA, and IIB were isolated from ''Streptomyces capreolus'' by Herr and co-workers at Eli Lilly.[2] Shiba and co-workers then completed the syntheses of capreomycins IA and IB.[3] The synthesis of capreomycin IB has been simplified to a 27 step synthesis route proposed by DeMong and Williams.[4]

'''Structures of the capreomycins'''

[[Image:Capreomycin0.gif]]

'''Scheme 1: Enolate-Aldimine Reaction'''

The asymmetric (2''S'',3''R'')-capreomycidine '''2''' was synthesised via an enolate-aldimine condensation between chiral glycinate (-) '''5''' and benzyl imine '''4'''.

[[Image:Capreomycin1.gif]]

'''Scheme 2: Completion of (2''S'',3''R'')-Capreomycidine'''

DeMong and Williams adapted titanium enolate chemistry to prepare an enantiomerically pure form of α-formylglycine dimethylacetal '''11'''.

[[Image:Capreomycin2.gif]]

==Properties and structure==

==Uses==

==References==

1. http://www.netdoctor.co.uk/medicines/100000447.html

2. Herr, E. B.; Haney, M. E.; Pittenger, G. E.; Higgens, C. E. Proc. Ind. Acad. Sci. 1960, 69, 134.

3. (a) Shiba, T.; Nomoto, S.; Teshima, T.; Wakamiya, T. Tetrahedron Lett. 1976, 17, 3907-3910. (b) Nomoto, S.; Teshima, T.; Wakamiya, T.; Shiba, T. J. Antibiot. 1977, 30, 955-959. (c) Nomoto, S.; Teshima, T.; Wakamiya, T.; Shiba, T. Tetrahedron 1978, 34, 921-927.

4. DeMong, D. E.; Williams, R. M.; J. Am. Chem. Soc., 125 (28), 8561-8565, 2003.

File:Capreomycin2.gif

2006-10-24T12:49:16Z

Ylt05:

It:Capreomycin

2006-10-24T12:46:48Z

Ylt05: added part of synthesis

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Substructure of Capreomycin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:Capreomycin.gif|200px|{{PAGENAME}}]]
|-
! {{chembox header}} colspan="3" | Possible R groups
|-
| colspan="1" |'''Analogue'''
| colspan="1" |'''R1'''
| colspan="1" |'''R2'''
|-
| colspan="1" |Capreomycin IA|| colspan="1" | OH || colspan="1" | β-Lys
|-
| colspan="1" |Capreomycin IB|| colspan="1" | H || colspan="1" |β-Lys
|-
| colspan="1" |Capreomycin IIA|| colspan="1" | OH || colspan="1" | NH2
|-
| colspan="1" |Capreomycin IIB|| colspan="1" | H || colspan="1" | NH2
|-
! {{chembox header}} colspan="3" |3D structure
|-
| align="center" colspan="3" bgcolor="#ffffff" | <jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 100; cpk off;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>HEADER CSD ENTRY XICKAV
CRYST1 8.5594 6.0337 11.0220 90.00 105.97 90.00 P21/c
SCALE1 0.116831 -0.000000 0.033428 0.000000
SCALE2 -0.000000 0.165736 -0.000000 0.000000
SCALE3 -0.000000 0.000000 0.094368 0.000000

ATOM 1 N 0 9.635 0.272 1.431 0.00 0.00 N+0

ATOM 2 C 0 8.738 0.894 0.719 0.00 0.00 C+0

ATOM 3 N 0 8.904 2.212 0.324 0.00 0.00 N+0

ATOM 4 C 0 7.736 3.102 0.425 0.00 0.00 C+0

ATOM 5 C 0 6.537 2.414 -0.237 0.00 0.00 C+0

ATOM 6 C 0 6.318 1.045 0.416 0.00 0.00 C+0

ATOM 7 C 0 5.194 0.303 -0.309 0.00 0.00 C+0

ATOM 8 C 0 4.977 -1.046 0.331 0.00 0.00 C+0

ATOM 9 N 0 4.240 -1.977 -0.351 0.00 0.00 N+0

ATOM 10 C 0 4.005 -3.241 0.391 0.00 0.00 C+0

ATOM 11 C 0 2.830 -3.973 -0.261 0.00 0.00 C+0

ATOM 12 C 0 1.532 -3.357 0.196 0.00 0.00 C+0

ATOM 13 N 0 0.356 -3.942 -0.195 0.00 0.00 N+0

ATOM 14 C 0 -0.864 -3.279 0.329 0.00 0.00 C+0

ATOM 15 C 0 -1.061 -1.985 -0.418 0.00 0.00 C+0

ATOM 16 N 0 -1.996 -1.100 0.026 0.00 0.00 N+0

ATOM 17 C 0 -2.119 0.158 -0.745 0.00 0.00 C+0

ATOM 18 C 0 -3.314 0.964 -0.232 0.00 0.00 C+0

ATOM 19 N 0 -4.539 0.176 -0.390 0.00 0.00 N+0

ATOM 20 C 0 -5.724 0.688 -0.003 0.00 0.00 C+0

ATOM 21 C 0 -6.984 -0.122 -0.166 0.00 0.00 C+0

ATOM 22 C 0 -8.179 0.684 0.347 0.00 0.00 C+0

ATOM 23 N 0 -8.296 1.930 -0.421 0.00 0.00 N+0

ATOM 24 C 0 -9.458 -0.139 0.182 0.00 0.00 C+0

ATOM 25 C 0 -10.653 0.667 0.695 0.00 0.00 C+0

ATOM 26 C 0 -11.932 -0.156 0.530 0.00 0.00 C+0

ATOM 27 N 0 -13.080 0.618 1.023 0.00 0.00 N+0

ATOM 28 O 0 -5.777 1.801 0.477 0.00 0.00 O+0

ATOM 29 C 0 -0.847 0.952 -0.552 0.00 0.00 C+0

ATOM 30 N 0 0.339 0.319 -0.813 0.00 0.00 N+0

ATOM 31 O 0 -0.875 2.106 -0.181 0.00 0.00 O+0

ATOM 32 O 0 -0.396 -1.736 -1.401 0.00 0.00 O+0

ATOM 33 C 0 -2.076 -4.187 0.113 0.00 0.00 C+0

ATOM 34 O 0 -1.874 -5.422 0.803 0.00 0.00 O+0

ATOM 35 O 0 1.529 -2.365 0.894 0.00 0.00 O+0

ATOM 36 N 0 2.936 -3.864 -1.722 0.00 0.00 N+0

ATOM 37 O 0 5.443 -1.299 1.422 0.00 0.00 O+0

ATOM 38 N 0 3.935 1.072 -0.199 0.00 0.00 N+0

ATOM 39 C 0 2.805 0.417 -0.585 0.00 0.00 C+0

ATOM 40 C 0 1.503 1.067 -0.452 0.00 0.00 C+0

ATOM 41 C 0 1.402 2.335 -0.002 0.00 0.00 C+0

ATOM 42 N 0 0.611 3.243 -0.671 0.00 0.00 N+0

ATOM 43 C 0 0.411 4.472 -0.155 0.00 0.00 C+0

ATOM 44 N 0 -0.362 5.360 -0.811 0.00 0.00 N+0

ATOM 45 O 0 0.928 4.779 0.901 0.00 0.00 O+0

ATOM 46 O 0 2.880 -0.709 -1.042 0.00 0.00 O+0

ATOM 47 N 0 7.569 0.269 0.311 0.00 0.00 N+0

ATOM 48 H 0 10.446 0.733 1.699 0.00 0.00 H+0

ATOM 49 H 0 9.757 2.536 -0.006 0.00 0.00 H+0

ATOM 50 H 0 7.514 3.296 1.474 0.00 0.00 H+0

ATOM 51 H 0 7.947 4.042 -0.087 0.00 0.00 H+0

ATOM 52 H 0 5.646 3.027 -0.104 0.00 0.00 H+0

ATOM 53 H 0 6.733 2.283 -1.301 0.00 0.00 H+0

ATOM 54 H 0 6.051 1.178 1.465 0.00 0.00 H+0

ATOM 55 H 0 5.457 0.173 -1.359 0.00 0.00 H+0

ATOM 56 H 0 3.900 -1.823 -1.246 0.00 0.00 H+0

ATOM 57 H 0 4.897 -3.865 0.345 0.00 0.00 H+0

ATOM 58 H 0 3.765 -3.016 1.431 0.00 0.00 H+0

ATOM 59 H 0 2.854 -5.025 0.027 0.00 0.00 H+0

ATOM 60 H 0 0.324 -4.725 -0.766 0.00 0.00 H+0

ATOM 61 H 0 -0.741 -3.073 1.392 0.00 0.00 H+0

ATOM 62 H 0 -2.549 -1.282 0.801 0.00 0.00 H+0

ATOM 63 H 0 -2.256 -0.070 -1.802 0.00 0.00 H+0

ATOM 64 H 0 -3.167 1.200 0.823 0.00 0.00 H+0

ATOM 65 H 0 -3.401 1.889 -0.802 0.00 0.00 H+0

ATOM 66 H 0 -4.497 -0.714 -0.774 0.00 0.00 H+0

ATOM 67 H 0 -7.131 -0.358 -1.220 0.00 0.00 H+0

ATOM 68 H 0 -6.898 -1.047 0.404 0.00 0.00 H+0

ATOM 69 H 0 -8.032 0.919 1.402 0.00 0.00 H+0

ATOM 70 H 0 -8.429 1.665 -1.386 0.00 0.00 H+0

ATOM 71 H 0 -9.150 2.376 -0.122 0.00 0.00 H+0

ATOM 72 H 0 -9.605 -0.375 -0.872 0.00 0.00 H+0

ATOM 73 H 0 -9.372 -1.064 0.752 0.00 0.00 H+0

ATOM 74 H 0 -10.507 0.903 1.749 0.00 0.00 H+0

ATOM 75 H 0 -10.740 1.592 0.125 0.00 0.00 H+0

ATOM 76 H 0 -12.079 -0.391 -0.524 0.00 0.00 H+0

ATOM 77 H 0 -11.846 -1.081 1.100 0.00 0.00 H+0

ATOM 78 H 0 -13.896 0.040 0.894 0.00 0.00 H+0

ATOM 79 H 0 -12.952 0.723 2.018 0.00 0.00 H+0

ATOM 80 H 0 0.386 -0.565 -1.210 0.00 0.00 H+0

ATOM 81 H 0 -2.970 -3.697 0.498 0.00 0.00 H+0

ATOM 82 H 0 -2.198 -4.382 -0.953 0.00 0.00 H+0

ATOM 83 H 0 -2.659 -5.964 0.641 0.00 0.00 H+0

ATOM 84 H 0 2.146 -4.359 -2.107 0.00 0.00 H+0

ATOM 85 H 0 2.808 -2.890 -1.950 0.00 0.00 H+0

ATOM 86 H 0 3.915 1.985 0.128 0.00 0.00 H+0

ATOM 87 H 0 1.940 2.638 0.884 0.00 0.00 H+0

ATOM 88 H 0 0.198 2.998 -1.514 0.00 0.00 H+0

ATOM 89 H 0 -0.506 6.245 -0.439 0.00 0.00 H+0

ATOM 90 H 0 -0.775 5.115 -1.653 0.00 0.00 H+0

ATOM 91 H 0 7.571 -0.641 -0.025 0.00 0.00 H+0

CONECT 1 2 48 0 0 NONE 96

CONECT 2 1 47 3 0 NONE 97

CONECT 3 2 4 49 0 NONE 98

CONECT 4 3 5 50 51 NONE 99

CONECT 5 4 6 52 53 NONE 100

CONECT 6 5 7 47 54 NONE 101

CONECT 7 6 8 38 55 NONE 102

CONECT 8 7 9 37 0 NONE 103

CONECT 9 8 10 56 0 NONE 104

CONECT 10 9 11 57 58 NONE 105

CONECT 11 10 12 36 59 NONE 106

CONECT 12 11 13 35 0 NONE 107

CONECT 13 12 14 60 0 NONE 108

CONECT 14 13 15 33 61 NONE 109

CONECT 15 14 16 32 0 NONE 110

CONECT 16 15 17 62 0 NONE 111

CONECT 17 16 18 29 63 NONE 112

CONECT 18 17 19 64 65 NONE 113

CONECT 19 18 20 66 0 NONE 114

CONECT 20 19 21 28 0 NONE 115

CONECT 21 20 22 67 68 NONE 116

CONECT 22 21 23 24 69 NONE 117

CONECT 23 22 70 71 0 NONE 118

CONECT 24 22 25 72 73 NONE 119

CONECT 25 24 26 74 75 NONE 120

CONECT 26 25 27 76 77 NONE 121

CONECT 27 26 78 79 0 NONE 122

CONECT 28 20 0 0 0 NONE 123

CONECT 29 17 30 31 0 NONE 124

CONECT 30 29 40 80 0 NONE 125

CONECT 31 29 0 0 0 NONE 126

CONECT 32 15 0 0 0 NONE 127

CONECT 33 14 34 81 82 NONE 128

CONECT 34 33 83 0 0 NONE 129

CONECT 35 12 0 0 0 NONE 130

CONECT 36 11 84 85 0 NONE 131

CONECT 37 8 0 0 0 NONE 132

CONECT 38 7 39 86 0 NONE 133

CONECT 39 38 40 46 0 NONE 134

CONECT 40 39 30 41 0 NONE 135

CONECT 41 40 42 87 0 NONE 136

CONECT 42 41 43 88 0 NONE 137

CONECT 43 42 44 45 0 NONE 138

CONECT 44 43 89 90 0 NONE 139

CONECT 45 43 0 0 0 NONE 140

CONECT 46 39 0 0 0 NONE 141

CONECT 47 6 2 91 0 NONE 142

NONE 143
END</inlineContents>
</jmolApplet>
</jmol>
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|
|-
| colspan="1" |Auto name
| colspan="2" |
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" | C25H43N13O8
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |?
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |653.70 g/mol
|-
| colspan="1" |Appearance
| colspan="2" |
|-
|colspan="1" |Beilstein Registry number
| colspan="2" | 876587
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" | 61394-77-2
|-
! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Density Density] and [http://en.wikipedia.org/wiki/Phase_%28matter%29 Phase (matter)|phase]
| colspan="2" | g/cm
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility] in [ http://en.wikipedia.org/wiki/Water_%28molecule%29 Water_(molecule)|water]
| colspan="2" |
|-
| Other solvents
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Melting_point Melting point]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Boiling_point Boiling point]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K'') 
| colspan="2" |?
|-
! {{chembox header}} colspan="3"| Structure
|-
| [http://en.wikipedia.org/wiki/Crystal_structure Crystal structure] 
| colspan="2"|
|-
| [http://en.wikipedia.org/wiki/Dipole#Molecular_dipoles Dipole moment]
| colspan="2" |? [http://en.wikipedia.org/wiki/Debye D]
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| [http://en.wikipedia.org/wiki/Material_safety_data_sheet MSDS]
| colspan="2" |[[{{PAGENAME}} (data page)#Material Safety Data Sheet|External MSDS]] 
|-
| 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" |
|-
| [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" | [[{{PAGENAME}} (data page)|Supplementary data page]]
|-
| Structure and properties
| colspan="2" |
|-
| Thermodynamic data
| colspan="2" |
|-
| Spectral data
| colspan="2" | [[UV/VIS spectroscopy|UV]], [[Infrared spectroscopy|IR]], [[nuclear magnetic resonance spectroscopy|NMR]], [[Mass spectrometry|MS]]
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|-
| {{chembox header}} colspan="3"| Except where noted otherwise, data are given for materials in their [http://en.wikipedia.org/wiki/Standard_state standard state (at 25 °C, 100 kPa)] [http://en.wikipedia.org/wiki/Wikipedia:Chemical_infobox Infobox disclaimer and references]]
|-
|}

'''Capreomycin''' is an antibiotic in the family of [http://en.wikipedia.org/wiki/Aminoglycosides aminoglycosides]. Capreomycin is effective against a number of [http://en.wikipedia.org/wiki/Gram_positive Gram-positive] and [http://en.wikipedia.org/wiki/Gram-negative Gram-negative] bacteria, and finds particular application against [http://en.wikipedia.org/wiki/Mycobacterium mycobacteria] such as [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] which causes [http://en.wikipedia.org/wiki/Tuberculosis tuberculosis].

Capreomycins have been particularly successful in treating the various strains of the bacterium ''Mycobacterium tuberculosis'', and hence are extremely valuable to patients who do not respond to drugs commonly used to treat TB. Capreomycin is normally prescribed together with other medications, preventing the patient from developing sole resistance to the drug. Capreomycin is injected into the patient, as it cannot be absorbed through the digestive tract. It causes the malfunction of the protein production of the bacteria, effectively eliminating the bacteria from the patient’s body.[http://www.netdoctor.co.uk/medicines/100000447.html]

==Synthesis==

In 1959, the tuberculostatic cyclic peptide antibiotics capreomycins IA, IB, IIA, and IIB were isolated from ''Streptomyces capreolus'' by Herr and co-workers at Eli Lilly.[2] Shiba and co-workers then completed the syntheses of capreomycins IA and IB.[3] The synthesis of capreomycin IB has been simplified to a 27 step synthesis route proposed by DeMong and Williams.[4]

'''Structures of the capreomycins'''

[[Image:Capreomycin0.gif]]

'''Scheme 1: Enolate-Aldimine Reaction'''

The asymmetric (2S,3R)-capreomycidine '''2''' was synthesised via an enolate-aldimine condensation between chiral glycinate (-) '''5''' and benzyl imine '''4'''.

[[Image:Capreomycin1.gif]]

==Properties and structure==

==Uses==

==References==

1. http://www.netdoctor.co.uk/medicines/100000447.html

2. Herr, E. B.; Haney, M. E.; Pittenger, G. E.; Higgens, C. E. Proc. Ind. Acad. Sci. 1960, 69, 134.

3. (a) Shiba, T.; Nomoto, S.; Teshima, T.; Wakamiya, T. Tetrahedron Lett. 1976, 17, 3907-3910. (b) Nomoto, S.; Teshima, T.; Wakamiya, T.; Shiba, T. J. Antibiot. 1977, 30, 955-959. (c) Nomoto, S.; Teshima, T.; Wakamiya, T.; Shiba, T. Tetrahedron 1978, 34, 921-927.

4. DeMong, D. E.; Williams, R. M.; J. Am. Chem. Soc., 125 (28), 8561 -8565, 2003.

It:Capreomycin

2006-10-24T12:45:45Z

Ylt05:

{| class="toccolours" border="1" style="float: right; clear: right; margin: 0 0 1em 1em; border-collapse: collapse;"
! {{chembox header}} colspan="3" |Substructure of Capreomycin
|-
| align="center" colspan="3" bgcolor="#ffffff" | [[Image:Capreomycin.gif|200px|{{PAGENAME}}]]
|-
! {{chembox header}} colspan="3" | Possible R groups
|-
| colspan="1" |'''Analogue'''
| colspan="1" |'''R1'''
| colspan="1" |'''R2'''
|-
| colspan="1" |Capreomycin IA|| colspan="1" | OH || colspan="1" | β-Lys
|-
| colspan="1" |Capreomycin IB|| colspan="1" | H || colspan="1" |β-Lys
|-
| colspan="1" |Capreomycin IIA|| colspan="1" | OH || colspan="1" | NH2
|-
| colspan="1" |Capreomycin IIB|| colspan="1" | H || colspan="1" | NH2
|-
! {{chembox header}} colspan="3" |3D structure
|-
| align="center" colspan="3" bgcolor="#ffffff" | <jmol>
<jmolApplet>
<size>200</size>
<color>white</color>
<script>zoom 100; cpk off;frame 1; move 10 -20 10 0 0 0 0 0 3; delay 1;</script>
<inlineContents>HEADER CSD ENTRY XICKAV
CRYST1 8.5594 6.0337 11.0220 90.00 105.97 90.00 P21/c
SCALE1 0.116831 -0.000000 0.033428 0.000000
SCALE2 -0.000000 0.165736 -0.000000 0.000000
SCALE3 -0.000000 0.000000 0.094368 0.000000

ATOM 1 N 0 9.635 0.272 1.431 0.00 0.00 N+0

ATOM 2 C 0 8.738 0.894 0.719 0.00 0.00 C+0

ATOM 3 N 0 8.904 2.212 0.324 0.00 0.00 N+0

ATOM 4 C 0 7.736 3.102 0.425 0.00 0.00 C+0

ATOM 5 C 0 6.537 2.414 -0.237 0.00 0.00 C+0

ATOM 6 C 0 6.318 1.045 0.416 0.00 0.00 C+0

ATOM 7 C 0 5.194 0.303 -0.309 0.00 0.00 C+0

ATOM 8 C 0 4.977 -1.046 0.331 0.00 0.00 C+0

ATOM 9 N 0 4.240 -1.977 -0.351 0.00 0.00 N+0

ATOM 10 C 0 4.005 -3.241 0.391 0.00 0.00 C+0

ATOM 11 C 0 2.830 -3.973 -0.261 0.00 0.00 C+0

ATOM 12 C 0 1.532 -3.357 0.196 0.00 0.00 C+0

ATOM 13 N 0 0.356 -3.942 -0.195 0.00 0.00 N+0

ATOM 14 C 0 -0.864 -3.279 0.329 0.00 0.00 C+0

ATOM 15 C 0 -1.061 -1.985 -0.418 0.00 0.00 C+0

ATOM 16 N 0 -1.996 -1.100 0.026 0.00 0.00 N+0

ATOM 17 C 0 -2.119 0.158 -0.745 0.00 0.00 C+0

ATOM 18 C 0 -3.314 0.964 -0.232 0.00 0.00 C+0

ATOM 19 N 0 -4.539 0.176 -0.390 0.00 0.00 N+0

ATOM 20 C 0 -5.724 0.688 -0.003 0.00 0.00 C+0

ATOM 21 C 0 -6.984 -0.122 -0.166 0.00 0.00 C+0

ATOM 22 C 0 -8.179 0.684 0.347 0.00 0.00 C+0

ATOM 23 N 0 -8.296 1.930 -0.421 0.00 0.00 N+0

ATOM 24 C 0 -9.458 -0.139 0.182 0.00 0.00 C+0

ATOM 25 C 0 -10.653 0.667 0.695 0.00 0.00 C+0

ATOM 26 C 0 -11.932 -0.156 0.530 0.00 0.00 C+0

ATOM 27 N 0 -13.080 0.618 1.023 0.00 0.00 N+0

ATOM 28 O 0 -5.777 1.801 0.477 0.00 0.00 O+0

ATOM 29 C 0 -0.847 0.952 -0.552 0.00 0.00 C+0

ATOM 30 N 0 0.339 0.319 -0.813 0.00 0.00 N+0

ATOM 31 O 0 -0.875 2.106 -0.181 0.00 0.00 O+0

ATOM 32 O 0 -0.396 -1.736 -1.401 0.00 0.00 O+0

ATOM 33 C 0 -2.076 -4.187 0.113 0.00 0.00 C+0

ATOM 34 O 0 -1.874 -5.422 0.803 0.00 0.00 O+0

ATOM 35 O 0 1.529 -2.365 0.894 0.00 0.00 O+0

ATOM 36 N 0 2.936 -3.864 -1.722 0.00 0.00 N+0

ATOM 37 O 0 5.443 -1.299 1.422 0.00 0.00 O+0

ATOM 38 N 0 3.935 1.072 -0.199 0.00 0.00 N+0

ATOM 39 C 0 2.805 0.417 -0.585 0.00 0.00 C+0

ATOM 40 C 0 1.503 1.067 -0.452 0.00 0.00 C+0

ATOM 41 C 0 1.402 2.335 -0.002 0.00 0.00 C+0

ATOM 42 N 0 0.611 3.243 -0.671 0.00 0.00 N+0

ATOM 43 C 0 0.411 4.472 -0.155 0.00 0.00 C+0

ATOM 44 N 0 -0.362 5.360 -0.811 0.00 0.00 N+0

ATOM 45 O 0 0.928 4.779 0.901 0.00 0.00 O+0

ATOM 46 O 0 2.880 -0.709 -1.042 0.00 0.00 O+0

ATOM 47 N 0 7.569 0.269 0.311 0.00 0.00 N+0

ATOM 48 H 0 10.446 0.733 1.699 0.00 0.00 H+0

ATOM 49 H 0 9.757 2.536 -0.006 0.00 0.00 H+0

ATOM 50 H 0 7.514 3.296 1.474 0.00 0.00 H+0

ATOM 51 H 0 7.947 4.042 -0.087 0.00 0.00 H+0

ATOM 52 H 0 5.646 3.027 -0.104 0.00 0.00 H+0

ATOM 53 H 0 6.733 2.283 -1.301 0.00 0.00 H+0

ATOM 54 H 0 6.051 1.178 1.465 0.00 0.00 H+0

ATOM 55 H 0 5.457 0.173 -1.359 0.00 0.00 H+0

ATOM 56 H 0 3.900 -1.823 -1.246 0.00 0.00 H+0

ATOM 57 H 0 4.897 -3.865 0.345 0.00 0.00 H+0

ATOM 58 H 0 3.765 -3.016 1.431 0.00 0.00 H+0

ATOM 59 H 0 2.854 -5.025 0.027 0.00 0.00 H+0

ATOM 60 H 0 0.324 -4.725 -0.766 0.00 0.00 H+0

ATOM 61 H 0 -0.741 -3.073 1.392 0.00 0.00 H+0

ATOM 62 H 0 -2.549 -1.282 0.801 0.00 0.00 H+0

ATOM 63 H 0 -2.256 -0.070 -1.802 0.00 0.00 H+0

ATOM 64 H 0 -3.167 1.200 0.823 0.00 0.00 H+0

ATOM 65 H 0 -3.401 1.889 -0.802 0.00 0.00 H+0

ATOM 66 H 0 -4.497 -0.714 -0.774 0.00 0.00 H+0

ATOM 67 H 0 -7.131 -0.358 -1.220 0.00 0.00 H+0

ATOM 68 H 0 -6.898 -1.047 0.404 0.00 0.00 H+0

ATOM 69 H 0 -8.032 0.919 1.402 0.00 0.00 H+0

ATOM 70 H 0 -8.429 1.665 -1.386 0.00 0.00 H+0

ATOM 71 H 0 -9.150 2.376 -0.122 0.00 0.00 H+0

ATOM 72 H 0 -9.605 -0.375 -0.872 0.00 0.00 H+0

ATOM 73 H 0 -9.372 -1.064 0.752 0.00 0.00 H+0

ATOM 74 H 0 -10.507 0.903 1.749 0.00 0.00 H+0

ATOM 75 H 0 -10.740 1.592 0.125 0.00 0.00 H+0

ATOM 76 H 0 -12.079 -0.391 -0.524 0.00 0.00 H+0

ATOM 77 H 0 -11.846 -1.081 1.100 0.00 0.00 H+0

ATOM 78 H 0 -13.896 0.040 0.894 0.00 0.00 H+0

ATOM 79 H 0 -12.952 0.723 2.018 0.00 0.00 H+0

ATOM 80 H 0 0.386 -0.565 -1.210 0.00 0.00 H+0

ATOM 81 H 0 -2.970 -3.697 0.498 0.00 0.00 H+0

ATOM 82 H 0 -2.198 -4.382 -0.953 0.00 0.00 H+0

ATOM 83 H 0 -2.659 -5.964 0.641 0.00 0.00 H+0

ATOM 84 H 0 2.146 -4.359 -2.107 0.00 0.00 H+0

ATOM 85 H 0 2.808 -2.890 -1.950 0.00 0.00 H+0

ATOM 86 H 0 3.915 1.985 0.128 0.00 0.00 H+0

ATOM 87 H 0 1.940 2.638 0.884 0.00 0.00 H+0

ATOM 88 H 0 0.198 2.998 -1.514 0.00 0.00 H+0

ATOM 89 H 0 -0.506 6.245 -0.439 0.00 0.00 H+0

ATOM 90 H 0 -0.775 5.115 -1.653 0.00 0.00 H+0

ATOM 91 H 0 7.571 -0.641 -0.025 0.00 0.00 H+0

CONECT 1 2 48 0 0 NONE 96

CONECT 2 1 47 3 0 NONE 97

CONECT 3 2 4 49 0 NONE 98

CONECT 4 3 5 50 51 NONE 99

CONECT 5 4 6 52 53 NONE 100

CONECT 6 5 7 47 54 NONE 101

CONECT 7 6 8 38 55 NONE 102

CONECT 8 7 9 37 0 NONE 103

CONECT 9 8 10 56 0 NONE 104

CONECT 10 9 11 57 58 NONE 105

CONECT 11 10 12 36 59 NONE 106

CONECT 12 11 13 35 0 NONE 107

CONECT 13 12 14 60 0 NONE 108

CONECT 14 13 15 33 61 NONE 109

CONECT 15 14 16 32 0 NONE 110

CONECT 16 15 17 62 0 NONE 111

CONECT 17 16 18 29 63 NONE 112

CONECT 18 17 19 64 65 NONE 113

CONECT 19 18 20 66 0 NONE 114

CONECT 20 19 21 28 0 NONE 115

CONECT 21 20 22 67 68 NONE 116

CONECT 22 21 23 24 69 NONE 117

CONECT 23 22 70 71 0 NONE 118

CONECT 24 22 25 72 73 NONE 119

CONECT 25 24 26 74 75 NONE 120

CONECT 26 25 27 76 77 NONE 121

CONECT 27 26 78 79 0 NONE 122

CONECT 28 20 0 0 0 NONE 123

CONECT 29 17 30 31 0 NONE 124

CONECT 30 29 40 80 0 NONE 125

CONECT 31 29 0 0 0 NONE 126

CONECT 32 15 0 0 0 NONE 127

CONECT 33 14 34 81 82 NONE 128

CONECT 34 33 83 0 0 NONE 129

CONECT 35 12 0 0 0 NONE 130

CONECT 36 11 84 85 0 NONE 131

CONECT 37 8 0 0 0 NONE 132

CONECT 38 7 39 86 0 NONE 133

CONECT 39 38 40 46 0 NONE 134

CONECT 40 39 30 41 0 NONE 135

CONECT 41 40 42 87 0 NONE 136

CONECT 42 41 43 88 0 NONE 137

CONECT 43 42 44 45 0 NONE 138

CONECT 44 43 89 90 0 NONE 139

CONECT 45 43 0 0 0 NONE 140

CONECT 46 39 0 0 0 NONE 141

CONECT 47 6 2 91 0 NONE 142

NONE 143
END</inlineContents>
</jmolApplet>
</jmol>
|-
! {{chembox header}} colspan="3" | General
|-
| colspan="1" |[http://en.wikipedia.org/wiki/IUPAC_nomenclature Systematic name]
| colspan="2"|
|-
| colspan="1" |Auto name
| colspan="2" |
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Chemical_formula Molecular formula]
| colspan="2" | C25H43N13O8
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Simplified_molecular_input_line_entry_specification SMILES]
| colspan="2" |?
|-
| colspan="1" |[http://en.wikipedia.org/wiki/Molar_mass Molar mass]
| colspan="2" |653.70 g/mol
|-
| colspan="1" |Appearance
| colspan="2" |
|-
|colspan="1" |Beilstein Registry number
| colspan="2" | 876587
|-
| colspan="1" |[http://en.wikipedia.org/wiki/CAS_registry_number CAS number]
| colspan="2" | 61394-77-2
|-
! {{chembox header}} colspan="3"| Properties
|-
| [http://en.wikipedia.org/wiki/Density Density] and [http://en.wikipedia.org/wiki/Phase_%28matter%29 Phase (matter)|phase]
| colspan="2" | g/cm
|-
| [http://en.wikipedia.org/wiki/Solubility Solubility] in [ http://en.wikipedia.org/wiki/Water_%28molecule%29 Water_(molecule)|water]
| colspan="2" |
|-
| Other solvents
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Melting_point Melting point]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Boiling_point Boiling point]
| colspan="2" |
|-
| [http://en.wikipedia.org/wiki/Acid_dissociation_constant Basicity] (p''K'') 
| colspan="2" |?
|-
! {{chembox header}} colspan="3"| Structure
|-
| [http://en.wikipedia.org/wiki/Crystal_structure Crystal structure] 
| colspan="2"|
|-
| [http://en.wikipedia.org/wiki/Dipole#Molecular_dipoles Dipole moment]
| colspan="2" |? [http://en.wikipedia.org/wiki/Debye D]
|-
! {{chembox header}} colspan="3" | Hazards 
|-
| [http://en.wikipedia.org/wiki/Material_safety_data_sheet MSDS]
| colspan="2" |[[{{PAGENAME}} (data page)#Material Safety Data Sheet|External MSDS]] 
|-
| 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" |
|-
| [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" | [[{{PAGENAME}} (data page)|Supplementary data page]]
|-
| Structure and properties
| colspan="2" |
|-
| Thermodynamic data
| colspan="2" |
|-
| Spectral data
| colspan="2" | [[UV/VIS spectroscopy|UV]], [[Infrared spectroscopy|IR]], [[nuclear magnetic resonance spectroscopy|NMR]], [[Mass spectrometry|MS]]
|-
! {{chembox header}} colspan="3" | Related compounds
|-
| Related compounds
| colspan="2" |
|-
| {{chembox header}} colspan="3"| Except where noted otherwise, data are given for materials in their [http://en.wikipedia.org/wiki/Standard_state standard state (at 25 °C, 100 kPa)] [http://en.wikipedia.org/wiki/Wikipedia:Chemical_infobox Infobox disclaimer and references]]
|-
|}

'''Capreomycin''' is an antibiotic in the family of [http://en.wikipedia.org/wiki/Aminoglycosides aminoglycosides]. Capreomycin is effective against a number of [http://en.wikipedia.org/wiki/Gram_positive Gram-positive] and [http://en.wikipedia.org/wiki/Gram-negative Gram-negative] bacteria, and finds particular application against [http://en.wikipedia.org/wiki/Mycobacterium mycobacteria] such as [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] which causes [http://en.wikipedia.org/wiki/Tuberculosis tuberculosis].

Capreomycins have been particularly successful in treating the various strains of the bacterium ''Mycobacterium tuberculosis'', and hence are extremely valuable to patients who do not respond to drugs commonly used to treat TB. Capreomycin is normally prescribed together with other medications, preventing the patient from developing sole resistance to the drug. Capreomycin is injected into the patient, as it cannot be absorbed through the digestive tract. It causes the malfunction of the protein production of the bacteria, effectively eliminating the bacteria from the patient’s body.[http://www.netdoctor.co.uk/medicines/100000447.html]

==Synthesis==

In 1959, the tuberculostatic cyclic peptide antibiotics capreomycins IA, IB, IIA, and IIB were isolated from ''Streptomyces capreolus'' by Herr and co-workers at Eli Lilly.[2] Shiba and co-workers then completed the syntheses of capreomycins IA and IB.[3] The synthesis of capreomycin IB has been simplified to a 27 step synthesis route proposed by DeMong and Williams.[4]

'''Structures of the capreomycins'''

[[Image:Capreomycin0.gif]]

'''Scheme 1: Enolate-Aldimine Reaction'''

The asymmetric (2S,3R)-capreomycidine was synthesised via an enolate-aldimine condensation between chiral glycinate (-) '''5''' and benzyl imine '''4'''.

[[Image:Capreomycin1.gif]]

==Properties and structure==

==Uses==

==References==

1. http://www.netdoctor.co.uk/medicines/100000447.html

2. Herr, E. B.; Haney, M. E.; Pittenger, G. E.; Higgens, C. E. Proc. Ind. Acad. Sci. 1960, 69, 134.

3. (a) Shiba, T.; Nomoto, S.; Teshima, T.; Wakamiya, T. Tetrahedron Lett. 1976, 17, 3907-3910. (b) Nomoto, S.; Teshima, T.; Wakamiya, T.; Shiba, T. J. Antibiot. 1977, 30, 955-959. (c) Nomoto, S.; Teshima, T.; Wakamiya, T.; Shiba, T. Tetrahedron 1978, 34, 921-927.

4. DeMong, D. E.; Williams, R. M.; J. Am. Chem. Soc., 125 (28), 8561 -8565, 2003.