【结 构 式】 |
【分子编号】12972 【品名】(8R,9S,10R,13S,14R)-14-Hydroxy-10,13-dimethyl-3-propoxy-1,2,7,8,9,10,11,12,13,14,15,16-dodecahydro-17H-cyclopenta[a]phenanthren-17-one 【CA登记号】 |
【 分 子 式 】C22H32O3 【 分 子 量 】344.49428 【元素组成】C 76.7% H 9.36% O 13.93% |
合成路线1
该中间体在本合成路线中的序号:(IVc)NKS-01 can be obtained by four similar ways: 1) The microbial hydroxylation of 4-androstene-3,17-dione (I) by a culture of Acremonium strictum NN-106 (FERM P-9143) gives 6beta,14alpha-dihydroxy-4-androstene-3,17-dione (II), which is then oxidized, either photochemically with oxygen in CHCl3 under sunlight , with MgO2 at room temperature (2) or with CrO3/H2SO4. 2) The selective microbial hydroxylation of (I) with a culture of Acremonium strictum NN-106 gives 14alpha-hydroxy-4-androstene-3,17-dione (III), which by alkylation of its enolic form is converted into 3-alkoxy-14alpha-hydroxy-3,5-androstadien-17-one (IV) (R = C1-3 alkyl). Finally, (IV) is oxidized with Jones' reagent (CrO3/H2SO4). 3) By oxidation of 3beta,14alpha-dihydroxy-5-androsten-17-one (V) with Jones' reagent (CrO3/H2SO4) in acetone or with K2Cr2O7 in acetic acid. 4) The microbial hydroxylation of (I) by a microorganism of the genus Myrothecium, such as Myrothecium sp. NK-928521 or natural or artificial mutants, gives (II), which is then oxidized with activated MgO2 in CHCl3 at room temperature.
【1】 Nakakoshi, M.; Yoshihama, M.; Nakamura, H.; et al. (Snow Brand Milk Products Co., Ltd.); New manufacturing method for 14alpha-hydroxy-4-androsten-3,6,17-trione. JP 9307687 . |
【2】 Graul, A.; Castaner, J.; NKS-01. Drugs Fut 1996, 21, 10, 1028. |
【3】 Yoshihama, M.; Tamura, K.; Miyata, N.; Nakayama, S.; Nakakoshi, M. (Snow Brand Milk Products Co., Ltd.); Novel androst-4-ene-3,17-dione derivs. and process for their preparation. JP 1988192794; JP 1988192795; JP 1988192796; JP 1988192797; US 4975368; WO 8805781 . |
【4】 Seya, M.; Nakamura, H.; Nakakoshi, M. (Snow Brand Milk Products Co., Ltd.); Process for the preparation of 14alpha-hydroxy-4-androsten-3,6,17-trione. JP 1991068596 . |
【5】 Nakakoshi, M.; Tamura, K.; Yoshihama, M.; Miyata, N. (Snow Brand Milk Products Co., Ltd.); Process for preparing 14alpha-hydroxy-4-androstene-3,6,17-trione. EP 0382162 . |
【6】 Yoshioka, H.; Asada, H.; Fujita, S. (Nippon Kayaku Co., Ltd.); Process for production of 6beta,14alpha-dihydroxy-4-androstene-3,17-dione. EP 0599658 . |
【7】 Yoshihama, M.; Nakakoshi, M.; Tamura, K.; Miyata, N.; Kawanishi, G.; Microbial production of two new dihydroxylated androstenedione derivatives by Acremonium strictum. J Ferment Bioeng 1989, 67, 4, 238-43. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(IVa) | 12970 | (8R,9S,10R,13S,14R)-14-Hydroxy-3-methoxy-10,13-dimethyl-1,2,7,8,9,10,11,12,13,14,15,16-dodecahydro-17H-cyclopenta[a]phenanthren-17-one | C20H28O3 | 详情 | 详情 | |
(IVb) | 12971 | (8R,9S,10R,13S,14R)-3-Ethoxy-14-hydroxy-10,13-dimethyl-1,2,7,8,9,10,11,12,13,14,15,16-dodecahydro-17H-cyclopenta[a]phenanthren-17-one | C21H30O3 | 详情 | 详情 | |
(IVc) | 12972 | (8R,9S,10R,13S,14R)-14-Hydroxy-10,13-dimethyl-3-propoxy-1,2,7,8,9,10,11,12,13,14,15,16-dodecahydro-17H-cyclopenta[a]phenanthren-17-one | C22H32O3 | 详情 | 详情 | |
(I) | 12967 | 4-Androstene-3,7-dione; Androstenedione; (8R,9S,10R,13S)-10,13-Dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione | 63-05-8 | C19H26O2 | 详情 | 详情 |
(II) | 12968 | (6R,8R,9S,10R,13S,14R)-6,14-Dihydroxy-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione | C19H26O4 | 详情 | 详情 | |
(III) | 12969 | (8R,9S,10R,13S,14R)-14-Hydroxy-10,13-dimethyl-7,8,9,10,11,12,13,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione | C19H26O3 | 详情 | 详情 | |
(V) | 12973 | (3S,8R,9S,10R,13S,14R)-3,14-Dihydroxy-10,13-dimethyl-1,2,3,4,7,8,9,10,11,12,13,14,15,16-tetradecahydro-17H-cyclopenta[a]phenanthren-17-one | C19H28O3 | 详情 | 详情 |