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【结 构 式】 
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【分子编号】34383 【品名】(8R,9S,10R,13S,14S,17S)-17-hydroxy-10,13,17-trimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one 【CA登记号】58-18-4 |
【 分 子 式 】C20H30O2 【 分 子 量 】302.457 【元素组成】C 79.42% H 10% O 10.58% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of 17beta-hydroxy-17-methylandrost-4-en-3-one (I) with thiophenol (A) and formaldehyde by means of triethylamine in refluxing ethanol gives 17beta-hydroxy-17-methy-4-(phenylthiomethyl)androst-4-en-3-one (II), which is desulfurized by treatment with Raney-Ni in water yielding 17beta-hydroxy-4,17-dimethylandrost-4-en-3-one (III). The reaction of (III) with methyl formate by means of sodium methoxide in methanol affords 17beta-hydroxy-4,17-dimethyl-2-hydroxymethyleneandrost-4-en-3-one (IV), which by cyclization with hydroxylamine in acetic acid-sodium acetate is converted into 4,17-dimethylandrosta-2,4-dieno[2,3-d]isoxazol-17beta-ol (V). The epoxidation of (V) with m-chloroperbenzoic acid in methylene chloride gives 4alpha,5alpha-epoxy-4,17-dimethylandrost-2-eno [2,3-d]isoxazol-17beta-ol (VI), which is finally isomerized by treatment with sodium methoxide in THF.
| 【1】 Christiansen, R.G. (Sanofi-Synthelabo); Steroid cyanoketones and intermediates. US 4160027 . |
| 【2】 Castaner, J.; Hillier, K.; Blancafort, P.; Serradell, M.N.; WIN-32,729. Drugs Fut 1982, 7, 9, 661. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 12951 | Benzenethiol; Phenylmercaptan; Phenylhydrosulfide | 108-98-5 | C6H6S | 详情 | 详情 |
| (I) | 34383 | (8R,9S,10R,13S,14S,17S)-17-hydroxy-10,13,17-trimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one | 58-18-4 | C20H30O2 | 详情 | 详情 |
| (II) | 37102 | (8R,9S,10R,13S,14S,17S)-17-hydroxy-10,13,17-trimethyl-4-[(phenylsulfanyl)methyl]-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one | C27H36O2S | 详情 | 详情 | |
| (III) | 37103 | (8R,9S,10R,13S,14S,17S)-17-hydroxy-4,10,13,17-tetramethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one | C21H32O2 | 详情 | 详情 | |
| (IV) | 37104 | (8R,9S,10R,13S,14S,17S)-17-hydroxy-2-[(Z)-hydroxymethylidene]-4,10,13,17-tetramethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-one | C22H32O3 | 详情 | 详情 | |
| (V) | 37105 | (1S,3aS,3bR,10aR,10bS,12aS)-1,6,10a,12a-tetramethyl-2,3,3a,3b,4,5,10,10a,10b,11,12,12a-dodecahydro-1H-cyclopenta[7,8]phenanthro[3,2-d]isoxazol-1-ol | C22H31NO2 | 详情 | 详情 | |
| (VI) | 37106 | (1S,3aS,3bS,5aS,6aS,10aR,10bS,12aS)-1,6a,10a,12a-tetramethyl-1,2,3,3a,3b,4,5,6a,10,10a,10b,11,12,12a-tetradecahydrocyclopenta[7,8]oxireno[2',3':10a,1]phenanthro[3,2-d]isoxazol-1-ol | C22H31NO3 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Ketalization of 17alpha-methyltestosterone (I) by means of ethylene glycol and p-toluenesulfonic acid provided the DELTA5(6)-ketal (II), and subsequent allylic oxidation of (II) with CrO3-3,5-dimethylpyrazole complex gave enone (III). Hydrogenation of the olefinic double bond of (III) afforded the saturated ketone (IV), which was reduced employing NaBH4 and CeCl3 to furnish an unseparable mixture of epimeric alcohols (Va-b). After removal of the ethylene ketal of (Va-b) with p-toluenesulfonic acid/acetone, the major 7beta-alcohol (VI) was isolated by flash chromatography. The 7beta-tosylate (VII) was then prepared by reaction of (VI) with p-tosyl chloride in pyridine. Finally, exchange of the tosylate group of (VII) with tetrabutylammonium fluoride yielded the desired 7alpha-fluoride.
| 【1】 Labaree, D.C.; et al.; 7alpha-Iodo and 7alpha-fluoro steroids as androgen receptor-mediated imaging agents. J Med Chem 1999, 42, 11, 2021. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 | |
| (Va) | 34387 | C22H36O4 | 详情 | 详情 | ||
| (Vb) | 34388 | C22H36O4 | 详情 | 详情 | ||
| (I) | 34383 | (8R,9S,10R,13S,14S,17S)-17-hydroxy-10,13,17-trimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3H-cyclopenta[a]phenanthren-3-one | 58-18-4 | C20H30O2 | 详情 | 详情 |
| (II) | 34384 | C22H34O3 | 详情 | 详情 | ||
| (III) | 34385 | C22H32O4 | 详情 | 详情 | ||
| (IV) | 34386 | C22H34O4 | 详情 | 详情 | ||
| (VI) | 34389 | (5S,7S,8R,9S,10S,13S,14S,17S)-7,17-dihydroxy-10,13,17-trimethylhexadecahydro-3H-cyclopenta[a]phenanthren-3-one | C20H32O3 | 详情 | 详情 | |
| (VII) | 34390 | (5S,7S,8R,9S,10S,13S,14S,17S)-17-hydroxy-10,13,17-trimethyl-3-oxohexadecahydro-1H-cyclopenta[a]phenanthren-7-yl 4-methylbenzenesulfonate | C27H38O5S | 详情 | 详情 |