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【结 构 式】 
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【分子编号】31006 【品名】5-(1-(3-carboxy-5-chloro-4-hydroxyphenyl)-4-[(3S,10S,13R,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl]-1-butenyl)-3-chloro-2-hydroxybenzoic acid 【CA登记号】 |
【 分 子 式 】C45H60Cl2O6 【 分 子 量 】767.8732 【元素组成】C 70.39% H 7.88% Cl 9.23% O 12.5% |
合成路线1
该中间体在本合成路线中的序号：(XV)The demethylation of intermediate (XI) with BBr3 and SMe2 in hot 1,2-dichloroethane gives the phenolic intermediate (cosalane, XV), which is simultaneously alkylated and esterified with 4-(bromomethyl)benzoic acid methyl ester (XVI) by means of K2CO3 in DMF yielding the tetrabenzylated intermediate (XVII). The final hydrolysis of the benzyl ester and methyl ester groups with KCN and K2CO3 in hot ethanol/water affords the target compound.
| 【1】 Cushman, M.; Insaf, S.; Paul, G.; Ruell, J.A.; De Clercq, E.; Schols, D.; Pannecouque, C.; Witvrouw, M.; Schaeffer, C.A.; Turpin, J.A.; Williamson, K.; Rice, W.G.; Extension of the polyanionic cosalane pharmacophore as a strategy for increasing anti-HIV potency. J Med Chem 1999, 42, 10, 1767. |
| 【2】 Bader, J.P.; Cushman, M.; Golebiewski, W.M.; Design and synthesis of cosalane, a novel anti-HIV agent. Bioorg Med Chem Lett 1993, 3, 8, 1739. |
| 【3】 Golebiewski, W.M.; McMahon, J.B.; Cushman, M.; et al.; Design, synthesis, and biological evaluation of cosalane, a novel anti-HIV agent which inhibits multiple features of virus reproduction. J Med Chem 1994, 37, 19, 3040. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 31005 | methyl 3-chloro-5-[3-chloro-4-methoxy-5-(methoxycarbonyl)benzyl]-2-methoxybenzoate | C19H18Cl2O6 | 详情 | 详情 | |
| (XV) | 31006 | 5-(1-(3-carboxy-5-chloro-4-hydroxyphenyl)-4-[(3S,10S,13R,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl]-1-butenyl)-3-chloro-2-hydroxybenzoic acid | C45H60Cl2O6 | 详情 | 详情 | |
| (XVI) | 14565 | methyl 4-(bromomethyl)benzoate | 2417-72-3 | C9H9BrO2 | 详情 | 详情 |
| (XVII) | 31007 | 4-(methoxycarbonyl)benzyl 3-chloro-5-(1-[3-chloro-4-[[4-(methoxycarbonyl)benzyl]oxy]-5-([[4-(methoxycarbonyl)benzyl]oxy]carbonyl)phenyl]-4-[(3S,10S,13R,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl]-1- | C81H92Cl2O14 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XV)The demethylation of intermediate (XI) with BBr3 and SMe2 in hot 1,2-dichloroethane gives the phenolic intermediate (cosalane, XV), which is simultaneously alkylated and esterified with 4-(bromomethyl)benzoic acid methyl ester (XVI) by means of K2CO3 in DMF yielding the tetrabenzylated intermediate (XVII). The hydrolysis of the benzyl ester and methyl ester groups with KCN and K2CO3 in hot ethanol/water affords the intermediate tetracarboxylic acid (XVIII), which is finally converted into the target sodium salt by reaction with Na2CO3 in methanol or ethanol.
| 【1】 Cushman, M.; Insaf, S.; Paul, G.; Ruell, J.A.; De Clercq, E.; Schols, D.; Pannecouque, C.; Witvrouw, M.; Schaeffer, C.A.; Turpin, J.A.; Williamson, K.; Rice, W.G.; Extension of the polyanionic cosalane pharmacophore as a strategy for increasing anti-HIV potency. J Med Chem 1999, 42, 10, 1767. |
| 【2】 Bader, J.P.; Cushman, M.; Golebiewski, W.M.; Design and synthesis of cosalane, a novel anti-HIV agent. Bioorg Med Chem Lett 1993, 3, 8, 1739. |
| 【3】 Golebiewski, W.M.; McMahon, J.B.; Cushman, M.; et al.; Design, synthesis, and biological evaluation of cosalane, a novel anti-HIV agent which inhibits multiple features of virus reproduction. J Med Chem 1994, 37, 19, 3040. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 31005 | methyl 3-chloro-5-[3-chloro-4-methoxy-5-(methoxycarbonyl)benzyl]-2-methoxybenzoate | C19H18Cl2O6 | 详情 | 详情 | |
| (XV) | 31006 | 5-(1-(3-carboxy-5-chloro-4-hydroxyphenyl)-4-[(3S,10S,13R,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl]-1-butenyl)-3-chloro-2-hydroxybenzoic acid | C45H60Cl2O6 | 详情 | 详情 | |
| (XVI) | 14565 | methyl 4-(bromomethyl)benzoate | 2417-72-3 | C9H9BrO2 | 详情 | 详情 |
| (XVII) | 31007 | 4-(methoxycarbonyl)benzyl 3-chloro-5-(1-[3-chloro-4-[[4-(methoxycarbonyl)benzyl]oxy]-5-([[4-(methoxycarbonyl)benzyl]oxy]carbonyl)phenyl]-4-[(3S,10S,13R,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl]-1- | C81H92Cl2O14 | 详情 | 详情 | |
| (XVIII) | 31008 | 2-[(4-carboxybenzyl)oxy]-5-(1-[3-carboxy-4-[(4-carboxybenzyl)oxy]-5-chlorophenyl]-4-[(3S,10S,13R,17R)-17-[(1R)-1,5-dimethylhexyl]-10,13-dimethylhexadecahydro-1H-cyclopenta[a]phenanthren-3-yl]-1-butenyl)-3-chlorobenzoic acid | C61H72Cl2O10 | 详情 | 详情 |