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【结 构 式】 
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【分子编号】53011 【品名】(7R,8S,9S,13R,14S,17R)-17-(2-hydroxyethyl)-7,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-ol 【CA登记号】n/a |
【 分 子 式 】C21H30O2 【 分 子 量 】314.468 【元素组成】C 80.21% H 9.62% O 10.18% |
合成路线1
该中间体在本合成路线中的序号：(XV)A different strategy for preparing the target 6-methylated steroid nucleus was based on the conjugate addition of an organocuprate reagent to a dienone. The intermediate hydroxy enone (IV) was acylated with isopropenyl acetate to produce the bis-acetate (XII). Bromination of (XII) with N-bromosuccinimide, followed by dehydrohalogenation with Li2CO3 and LiBr in refluxing DMF, gave rise to dienone (XIII). Conjugate addition of methyllithium to (XIII) in the presence of CuI afforded the methylated compound (XIV). Aromatization of the cyclohexenone system was achieved by oxidation with CuCl2. Subsequent acetate ester hydrolysis under basic conditions generated diol (XV), which was converted to the bis-mesylate (XVI) upon treatment with methanesulfonyl chloride and Et3N. Displacement of the aliphatic mesylate with vanillic acid diethylamide (VII) yielded ether (XVII). Then, simultaneous amide reduction and reductive cleavage of the aryl mesylate with LiAlH4 provided the title compound.
| 【1】 Peters, R.H.; Tanabe, M.; Chao, W.-R.; Johansson, J.G.; Ryan, K.J.; Liu, J. (SRI International); Synthesis of anti-estrogenic acid and other therapeutic steroids from 21-hydroxy-19-norpregna-4-en-3-one. WO 0158919 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 53001 | (8R,9S,13R,14S,17R)-17-(2-hydroxyethyl)-13-methyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one | n/a | C20H30O2 | 详情 | 详情 |
| (VII) | 53004 | N,N-diethyl-4-hydroxy-3-methoxybenzamide | n/a | C12H17NO3 | 详情 | 详情 |
| (XII) | 53003 | (7S,8S,9S,13R,14S,17R)-17-(2-hydroxyethyl)-3-isopropoxy-7,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-6-one | n/a | C24H34O3 | 详情 | 详情 |
| (XIII) | 53009 | 2-[(8S,9S,13R,14S,17R)-13-methyl-3-oxo-2,3,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethyl acetate | n/a | C22H30O3 | 详情 | 详情 |
| (XIV) | 53010 | 2-[(7R,8R,9S,13R,14S,17R)-7,13-dimethyl-3-oxo-2,3,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethyl acetate | n/a | C23H34O3 | 详情 | 详情 |
| (XV) | 53011 | (7R,8S,9S,13R,14S,17R)-17-(2-hydroxyethyl)-7,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-ol | n/a | C21H30O2 | 详情 | 详情 |
| (XVI) | 53012 | (7R,8S,9S,13R,14S,17R)-7,13-dimethyl-17-{2-[(methylsulfonyl)oxy]ethyl}-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl methanesulfonate | n/a | C23H34O6S2 | 详情 | 详情 |
| (XVII) | 53013 | (7R,8S,9S,13R,14S,17R)-17-(2-{4-[(diethylamino)carbonyl]-2-methoxyphenoxy}ethyl)-7,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl methanesulfonate | n/a | C34H47NO6S | 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 intermediate diol (XV) was also obtained by an alternative procedure. Aromatization of enone (IV) in the presence of isopropanol, I2 and O2 gave rise to the isopropoxy ketone (XVIII). The free hydroxyl group was then protected as the tetrahydropyranyl ether (V). Alkylation at the alpha position of the keto group of (V) , followed by acidic hydrolysis of the tetrahydropyranyl group, furnished the alpha-methyl ketone (VI). The keto group of (VI) was subsequently reduced by hydrogenation over Pd/C to afford (XIX). Further isopropyl ether cleavage with AlCl3 afforded diol (XV).
| 【1】 Peters, R.H.; Tanabe, M.; Chao, W.-R.; Johansson, J.G.; Ryan, K.J.; Liu, J. (SRI International); Synthesis of anti-estrogenic acid and other therapeutic steroids from 21-hydroxy-19-norpregna-4-en-3-one. WO 0158919 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 53001 | (8R,9S,13R,14S,17R)-17-(2-hydroxyethyl)-13-methyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one | n/a | C20H30O2 | 详情 | 详情 |
| (V) | 53002 | (8S,9S,13R,14S,17R)-3-isopropoxy-13-methyl-17-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-6-one | n/a | C28H40O4 | 详情 | 详情 |
| (VI) | 53003 | (7S,8S,9S,13R,14S,17R)-17-(2-hydroxyethyl)-3-isopropoxy-7,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-6-one | n/a | C24H34O3 | 详情 | 详情 |
| (XV) | 53011 | (7R,8S,9S,13R,14S,17R)-17-(2-hydroxyethyl)-7,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-ol | n/a | C21H30O2 | 详情 | 详情 |
| (XVIII) | 53014 | (8S,9S,13R,14S,17R)-17-(2-hydroxyethyl)-3-isopropoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-6-one | n/a | C23H32O3 | 详情 | 详情 |
| (XIX) | 53015 | 2-[(7R,8S,9S,13R,14S,17R)-3-isopropoxy-7,13-dimethyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl]-1-ethanol | n/a | C24H36O2 | 详情 | 详情 |