【结 构 式】 |
【分子编号】56608 【品名】(8S,10R,13S,14S,17S)-17-hydroxy-3-methoxy-10,13-dimethyl-2,7,8,10,12,13,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthrene-17-carbonitrile 【CA登记号】 |
【 分 子 式 】C21H27NO2 【 分 子 量 】325.45092 【元素组成】C 77.5% H 8.36% N 4.3% O 9.83% |
合成路线1
该中间体在本合成路线中的序号:(XVII)Reaction of 3-methoxyandrosta-3,5,9(11)-trien-17-one (XI) with KCN and AcOH in methanol gives a 1:1 mixture of the epimeric cyanohydrins (XVII) and (XVIII) and the desired b-cyano epimer (XVIII) is obtained in a 95% yield by selective crystallization under equilibrating conditions. Protection of the 17-OH group of (XVIII) with TMS-Cl and imidazole yields the silyl ether (XIX), which is reduced with DIBAL and AcOH to afford the carbaldehyde (XX). Reaction of compound (XX) with dibromomethane and LDA provides the dibromo derivative (XXI), which by reaction with more LDA gives the lithium enolate (XXII). Hydrolysis of enolate (XXII) in acid medium yields the a-bromoketone (XXIII), which is acylated with AcOH and TEA in hot acetone to afford the silylated steroid (XXIV). Finally, compound (XXIV) is deprotected by means of HF and TEA in dichloromethane.
【1】 Castaner, J.; Sorbera, L.A.; Leeson, P.A.; Bayes, M.; Anecortave Acetate. Drugs Fut 2002, 27, 11, 1039. |
【2】 Reid, J.G.; Debiak-Krook, T.; Corticoids from 17-oxosteroids. Tetrahedron Lett 1990, 31, 26, 3669. |
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) | 18040 | (8S,10R,13S,14S)-3-methoxy-10,13-dimethyl-1,2,7,8,10,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-17-one | C20H26O2 | 详情 | 详情 | |
(XVII) | 56608 | (8S,10R,13S,14S,17S)-17-hydroxy-3-methoxy-10,13-dimethyl-2,7,8,10,12,13,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthrene-17-carbonitrile | C21H27NO2 | 详情 | 详情 | |
(XVIII) | 56607 | (8S,10R,13S,14S,17R)-17-hydroxy-3-methoxy-10,13-dimethyl-2,7,8,10,12,13,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthrene-17-carbonitrile | C21H27NO2 | 详情 | 详情 | |
(XIX) | 56609 | (8S,10R,13S,14S,17R)-3-methoxy-10,13-dimethyl-17-[(trimethylsilyl)oxy]-2,7,8,10,12,13,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthrene-17-carbonitrile | C24H35NO2Si | 详情 | 详情 | |
(XX) | 56610 | (8S,10R,13S,14S,17R)-3-methoxy-10,13-dimethyl-17-[(trimethylsilyl)oxy]-2,7,8,10,12,13,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthrene-17-carbaldehyde | C24H36O3Si | 详情 | 详情 | |
(XXI) | 56611 | 2,2-dibromo-1-{(8S,10R,13S,14S,17R)-3-methoxy-10,13-dimethyl-17-[(trimethylsilyl)oxy]-2,7,8,10,12,13,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl}-1-ethanol | C25H38Br2O3Si | 详情 | 详情 | |
(XXII) | 56612 | lithium (Z)-2-bromo-1-{(8S,10R,13S,14S,17R)-3-methoxy-10,13-dimethyl-17-[(trimethylsilyl)oxy]-2,7,8,10,12,13,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthren-17-yl}-1-ethenolate | C25H36BrLiO3Si | 详情 | 详情 | |
(XXIII) | 56613 | (8S,10R,13S,14S,17R)-17-(2-bromoacetyl)-10,13-dimethyl-17-[(trimethylsilyl)oxy]-1,2,6,7,8,10,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one | C24H35BrO3Si | 详情 | 详情 | |
(XXIV) | 56614 | 2-{(8S,10R,13S,14S,17R)-10,13-dimethyl-3-oxo-17-[(trimethylsilyl)oxy]-2,3,6,7,8,10,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl}-2-oxoethyl acetate | C26H38O5Si | 详情 | 详情 |