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【结 构 式】

【分子编号】42865

【品名】(1aS,3S,5aR,7aS,8aS,9aS,10S,10aS)-10-chloro-3-hydroxy-5a,7a-dimethyltetradecahydro-2H-cyclopropa[4',5']cyclopenta[1',2':1,2]phenanthro[8a,9-b]oxiren-8(6H)-one

【CA登记号】

【 分 子 式 】C20H27ClO3

【 分 子 量 】350.88528

【元素组成】C 68.46% H 7.76% Cl 10.1% O 13.68%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(VII)

This compound has been obtained by different ways: 1. The fermentation of 3beta-hydroxy-15beta,16beta-methylene-5-androsten-17-one (I) or 3beta-acetoxy-15beta,16beta-methylene-5-androsten-17-one (II) with Botryodiplodia malorum gives the corresponding 3beta,7beta-dihydroxy derivative (III), which is regioselectively silylated with Tbdms-Cl and imidazole to yield the 3-beta-silylated compound (IV). The epoxidation of (IV) by means of tert-butyl hydroperoxide catalyzed by VO(acetonylacetonate)2 complex affords the corresponding epoxide (V), which is treated with PPh3 and CCl4 in dichloromethane to provide the 7-alpha-chloro derivative (VI). The desilylation of (VI) with HCl in THF/methanol gives the 3beta-hydroxy compound (VII), which is treated with Zn in AcOH/THF to yield 3beta, 5beta-dihydroxy-15beta,16beta-methylene-6-androsten-17-one (VIII) (1). The cyclopropanation of (VIII) with diiodomethane and Zn in hot ethyleneglycol dimethylether gives 3beta,5beta-dihydroxy-6beta,7beta:15beta,16beta-bismethyleneandrostan-17-one (IX), which is condensed with propargyl alcohol (X) by means of K-OEt in THF, yielding 17alpha-(3-hydroxy-1-propynyl)-6beta,7beta:15beta,16beta-bismethyleneandrostan-3,5beta,17beta-triol (XI). The hydrogenation of (XI) with H2 over Pd/C in THF/methanol/pyridine affords the corresponding 17alpha-(3-hydroxypropyl) derivative (XII), which is finally oxidized, lactonized and dehydrated by means of CrO3 in hot pyridine/water. 2. Alternatively, the 17alpha-(3-hydroxypropyl) derivative (XII) can be oxidized with RuCl3 and NaBrO3 in hot acetonitrile/water, giving the hydroxy carbolactone (XIII), which is finally dehydrated by means of Ts-OH in THF. 3. Similar synthetic pathways have been described replacing the Tbdms protecting group with either dimethyl(3-methylbutyl)silyl or tribenzylsilyl groups.

1 Angew Chem 1982, 94, 718-719.
2 Nickisch, K.; Wiechert, R.; Laurent, H.; Petzoldt, K.; Bittler, D. (Schering AG); Process for preparing 3beta,7beta-dihydroxy-DELTA5-steroids. DE 3042136; EP 0051143; JP 1982122798; US 4416985; US 4614616 .
3 Mohr, J.-T.; Nickisch, K. (Schering AG); Process for producing drospirenone (6beta,7beta;15beta,16beta-dimethylene-3-oxo-17alpha-preg-4-en-21,17-carbolactone, DRSP), as well as 7alpha-(3-hydroxy-1-propyl)-6beta,7beta;15beta,16beta-dimethylene-5beta-androstane-3beta,5,17beta-triol (ZK 92836) and . DE 19633685; US 6121465; WO 9806738 .
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) 42507 (2S,4aR,4bS,6aS,7aS,8aS,8bR,8cR)-2-hydroxy-4a,6a-dimethyl-2,3,4,4a,4b,5,6,6a,7a,8,8a,8b,8c,9-tetradecahydrocyclopropa[4,5]cyclopenta[1,2-a]phenanthren-7(1H)-one C20H28O2 详情 详情
(II) 42862 (2S,4aR,6aS,7aS,8aS)-4a,6a-dimethyl-7-oxo-1,2,3,4,4a,4b,5,6,6a,7,7a,8,8a,8b,8c,9-hexadecahydrocyclopropa[4,5]cyclopenta[1,2-a]phenanthren-2-yl acetate C22H30O3 详情 详情
(III) 42508 (2S,4aR,4bS,6aS,7aS,8aS,8bS,8cR,9R)-2,9-dihydroxy-4a,6a-dimethyl-2,3,4,4a,4b,5,6,6a,7a,8,8a,8b,8c,9-tetradecahydrocyclopropa[4,5]cyclopenta[1,2-a]phenanthren-7(1H)-one C20H28O3 详情 详情
(IV) 42863 (2S,4aR,6aS,7aS,8aS,9R)-2-[[tert-butyl(dimethyl)silyl]oxy]-9-hydroxy-4a,6a-dimethyl-2,3,4,4a,4b,5,6,6a,7a,8,8a,8b,8c,9-tetradecahydrocyclopropa[4,5]cyclopenta[1,2-a]phenanthren-7(1H)-one C26H42O3Si 详情 详情
(V) 42864 (1aS,3S,5aR,7aS,8aS,9aS,10R,10aR)-3-[[tert-butyl(dimethyl)silyl]oxy]-10-hydroxy-5a,7a-dimethyltetradecahydro-2H-cyclopropa[4',5']cyclopenta[1',2':1,2]phenanthro[8a,9-b]oxiren-8(6H)-one C26H42O4Si 详情 详情
(VI) 42510 (1aS,3S,5aR,5bS,7aS,8aS,9aS,9bS,9cR,10S,10aS)-10-chloro-5a,7a-dimethyl-8-oxohexadecahydro-2H-cyclopropa[4',5']cyclopenta[1',2':1,2]phenanthro[8a,9-b]oxiren-3-yl pivalate C25H35ClO4 详情 详情
(VII) 42865 (1aS,3S,5aR,7aS,8aS,9aS,10S,10aS)-10-chloro-3-hydroxy-5a,7a-dimethyltetradecahydro-2H-cyclopropa[4',5']cyclopenta[1',2':1,2]phenanthro[8a,9-b]oxiren-8(6H)-one C20H27ClO3 详情 详情
(VIII) 42512 (2S,4aR,4bS,6aS,7aS,8aS,8bR,8cR,10aR)-2,10a-dihydroxy-4a,6a-dimethyl-2,3,4,4a,4b,5,6,6a,7a,8,8a,8b,8c,10a-tetradecahydrocyclopropa[4,5]cyclopenta[1,2-a]phenanthren-7(1H)-one C20H28O3 详情 详情
(IX) 42513 (1aR,1bR,3S,5aR,5bS,7aS,8aS,9aS,9bR,9cR,9dR)-1b,3-dihydroxy-5a,7a-dimethyloctadecahydro-8H-cyclopropa[4,5]cyclopenta[1,2-a]cyclopropa[l]phenanthren-8-one C21H30O3 详情 详情
(X) 16664 Propargyl Alcohol; 2-propyn-1-ol 107-19-7 C3H4O 详情 详情
(XI) 42515 (1aR,3S,5aR,5bS,7aS,8S,8aS,9aS,9bR,9cR,9dR)-8-(3-hydroxy-1-propynyl)-5a,7a-dimethyloctadecahydro-1bH-cyclopropa[4,5]cyclopenta[1,2-a]cyclopropa[l]phenanthrene-1b,3,8-triol C24H34O4 详情 详情
(XII) 42516 (1aR,3S,5aR,5bS,7aS,8S,8aS,9aS,9bR,9cS,9dR)-8-(3-hydroxypropyl)-5a,7a-dimethyloctadecahydro-1bH-cyclopropa[4,5]cyclopenta[1,2-a]cyclopropa[l]phenanthrene-1b,3,8-triol C24H38O4 详情 详情
(XIII) 42517   C24H32O4 详情 详情
Extended Information