【结 构 式】 |
【药物名称】 【化学名称】3-O-(3,3-Dimethylsuccinyl)-28-O-(2,2-dimethylsuccinyl)lup-20(29)-en-3beta,28-diol 【CA登记号】332346-42-6 【 分 子 式 】C42H66O8 【 分 子 量 】698.98952 |
【开发单位】BBI Biotech Research Laboratories (Originator) 【药理作用】AIDS Medicines, Anti-HIV Agents, ANTIINFECTIVE THERAPY |
合成路线1
Reaction of betulin (I) and 2,2-dimethylsuccinic acid (II) in refluxing pyridine, followed by HPLC separation of the two products obtained, affords derivative (III). Protection of the carboxylic group of (III) is then performed by formation of the corresponding allyl ester derivative (V) by reaction with allyl bromide (IV) and K2CO3 in acetone. Separately, 2,2-dimethylsuccinic acid (II) is treated with allyl alcohol (VI) in refluxing pyridine to give an isomeric mixture of compounds from which allyl succinate derivative (VII) is chromatographically isolated. Formation of the corresponding acid chloride (VIII) is finally performed by treatment of (VII) with (COCl)2 in refluxing benzene. Condensation between alcohol (V) and acid chloride (VIII) by means of DMAP in CH2Cl2 provides compound (IX), which is finally converted into the target product by removal of the allyl protecting groups by means of Pd(Ph3P)4 and morpholine.
【1】 Chiyo, J.; Ikeshiro, Y.; Cosentino, L.M.; Kashiwada, Y.; Fowke, K.; Lee, K.H.; Okabe, H.; Nagao, T.; 3,28-Di-O-(dimethylsuccinyl)-betulin isomers as anti-HIV agents. Bioorg Med Chem Lett 2001, 11, 2, 183. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 50064 | (1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-(hydroxymethyl)-1-isopropenyl-5a,5b,8,8,11a-pentamethylicosahydro-1H-cyclopenta[a]chrysen-9-ol | C30H50O2 | 详情 | 详情 | |
(II) | 46622 | 2,2-dimethylsuccinic acid | C6H10O4 | 详情 | 详情 | |
(III) | 50065 | 4-[[(1R,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-hydroxy-1-isopropenyl-5a,5b,8,8,11a-pentamethylicosahydro-3aH-cyclopenta[a]chrysen-3-yl]methoxy]-3,3-dimethyl-4-oxobutyric acid | C36H58O5 | 详情 | 详情 | |
(IV) | 11463 | 3-Bromo-1-propene; 3-Bromopropene;allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
(V) | 50066 | 1-[[(1R,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-9-hydroxy-1-isopropenyl-5a,5b,8,8,11a-pentamethylicosahydro-3aH-cyclopenta[a]chrysen-3-yl]methyl] 4-allyl 2,2-dimethylsuccinate | C39H62O5 | 详情 | 详情 | |
(VI) | 12234 | 2-Propen-1-ol; Allyl alcohol | 107-18-6 | C3H6O | 详情 | 详情 |
(VII) | 50067 | 4-(allyloxy)-3,3-dimethyl-4-oxobutyric acid | C9H14O4 | 详情 | 详情 | |
(VIII) | 50068 | allyl 4-chloro-2,2-dimethyl-4-oxobutanoate | C9H13ClO3 | 详情 | 详情 | |
(IX) | 50069 | 4-[(1R,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-3a-([[4-(allyloxy)-2,2-dimethyl-4-oxobutanoyl]oxy]methyl)-1-isopropenyl-5a,5b,8,8,11a-pentamethylicosahydro-3aH-cyclopenta[a]chrysen-9-yl] 1-allyl 2,2-dimethylsuccinate | C48H74O8 | 详情 | 详情 |