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【结 构 式】 
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【分子编号】42856 【品名】(3S,8R,9S,10R,13S,14S)-16-formyl-10,13-dimethyl-17-(2H-1,2,3-triazol-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate 【CA登记号】 |
【 分 子 式 】C24H31N3O3 【 分 子 量 】409.52856 【元素组成】C 70.39% H 7.63% N 10.26% O 11.72% |
合成路线1
该中间体在本合成路线中的序号：(V)The Vilsmeier-Haack reaction of 3-beta-acetoxyandrost-5-en-17-one (I) using POCl3 and DMF produced a mixture of the vinyl chloride (II) and its formyl derivative (III). After chromatographic separation, the chlorine atom of (III) was displaced with 1,2,3-triazole (IV) to afford the desired 1-triazolyl compound (V) along with the 2-triazolyl regioisomer (VI), which were separated by flash chromatography. Cleavage of the formyl group from compound (V) was carried out by treatment with bis(triphenylphosphine)rhodium(I)carbonyl chloride and 1,3-bis(diphenylphosphino)propane in hot xylenes to furnish (VII). The acetate ester group was finally hydrolyzed with methanolic KOH.
| 【1】 Njar, V.C.O.; Grigoryev, D.N.; Long, B.J.; Kato, K.; Brodie, A.M.H.; Nnane, I.P.; Novel 17-azolyl steroids, potent inhibitors of human cytochrome 17alpha-hydroxylase-C17,20-lyase (P45017alpha): Potential agents for the treatment of prostate cancer. J Med Chem 1998, 41, 6, 902. |
| 【2】 Brodie, A.; Njar, V.C.O. (University of Maryland); 17-Azolyl steroids useful as androgen synthesis inhibitors. US 5994335 . |
| 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) | 20083 | Prasterone acetate;3b-Hydroxy-5-androstene-17-one acetate；Dehydroisoandrosterone acetate;Dehydroepiandrosterone 3-acetate;Dehydroepiandrosterone acetate;(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 853-23-6 | C21H30O3 | 详情 | 详情 |
| (II) | 42853 | (3S,8R,9S,10R,13S,14S)-17-chloro-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C21H29ClO2 | 详情 | 详情 | |
| (III) | 42854 | (3S,8R,9S,10R,13S,14S)-17-chloro-16-formyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C22H29ClO3 | 详情 | 详情 | |
| (IV) | 29404 | 1H-1,2,3-triazole | 288-36-8 | C2H3N3 | 详情 | 详情 |
| (V) | 42856 | (3S,8R,9S,10R,13S,14S)-16-formyl-10,13-dimethyl-17-(2H-1,2,3-triazol-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C24H31N3O3 | 详情 | 详情 | |
| (VI) | 42855 | (3S,8R,9S,10R,13S,14S)-16-formyl-10,13-dimethyl-17-(1H-1,2,3-triazol-1-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C24H31N3O3 | 详情 | 详情 | |
| (VII) | 42857 | (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-(1H-1,2,3-triazol-1-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C23H31N3O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)The Vilsmeier-Haack formylation of 3-beta-acetoxyandrost-5-en-17-one (I) with POCl3/DMF provides the desired chloro aldehyde (III) along with minor amounts of the vinyl chloride (II), which are separated by column chromatography. Condensation of (III) with 1,2,3-triazole (IV) affords two regioisomeric triazole derivatives, (V) and (VI). After chromatographic isolation of the required 1-triazolyl compound (VI), decarbonylation of the 16-formyl group employing a modified Wilkinson’s catalyst gives (VII). The hydrolysis of the acetate group of (VII) with KOH in methanol gives the corresponding alcohol (VIII) , which is finally oxidized with aluminum isopropoxide and 1-methyl-4-piperidone in refluxing xylene.
| 【1】 Njar, V.C.O.; Grigoryev, D.N.; Long, B.J.; Kato, K.; Brodie, A.M.H.; Nnane, I.P.; Novel 17-azolyl steroids, potent inhibitors of human cytochrome 17alpha-hydroxylase-C17,20-lyase (P45017alpha): Potential agents for the treatment of prostate cancer. J Med Chem 1998, 41, 6, 902. |
| 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) | 20083 | Prasterone acetate;3b-Hydroxy-5-androstene-17-one acetate；Dehydroisoandrosterone acetate;Dehydroepiandrosterone 3-acetate;Dehydroepiandrosterone acetate;(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-oxo-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | 853-23-6 | C21H30O3 | 详情 | 详情 |
| (II) | 42853 | (3S,8R,9S,10R,13S,14S)-17-chloro-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C21H29ClO2 | 详情 | 详情 | |
| (III) | 42854 | (3S,8R,9S,10R,13S,14S)-17-chloro-16-formyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C22H29ClO3 | 详情 | 详情 | |
| (IV) | 29404 | 1H-1,2,3-triazole | 288-36-8 | C2H3N3 | 详情 | 详情 |
| (V) | 42856 | (3S,8R,9S,10R,13S,14S)-16-formyl-10,13-dimethyl-17-(2H-1,2,3-triazol-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C24H31N3O3 | 详情 | 详情 | |
| (VI) | 42855 | (3S,8R,9S,10R,13S,14S)-16-formyl-10,13-dimethyl-17-(1H-1,2,3-triazol-1-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C24H31N3O3 | 详情 | 详情 | |
| (VII) | 42857 | (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-(1H-1,2,3-triazol-1-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl acetate | C23H31N3O2 | 详情 | 详情 | |
| (VIII) | 42858 | (3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-(1H-1,2,3-triazol-1-yl)-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-3-ol | C21H29N3O | 详情 | 详情 |