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【结 构 式】 
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【药物名称】Gestodene, SH-546, SHB-331 【化学名称】13-Ethyl-17-hydroxy-18,19-dinor-17alpha-pregna-4,15-dien-20-yn-3-one 【CA登记号】60282-87-3 【 分 子 式 】C21H26O2 【 分 子 量 】310.44017 |
【开发单位】Schering AG (Originator) 【药理作用】Bone Diseases, Treatment of, ENDOCRINE DRUGS, Gynecological Disorders, Treatment of , Hormone Replacement Therapy, METABOLIC DRUGS, Prevention of Osteoporosis, Progestogens |
合成路线1
18-Methyl-4-oestrene-3,17-dione (I) is hydroxylated by fermentation with Penicillium raistrickii giving the 15alpha-hydroxy compound (II), which is ketalized with 2,2-dimethylpropanediol (A), triethyl orthoformate and p-toluenesulfonic acid in CH2Cl2 giving a mixture of the DELTA(5-6) and DELTA(5-10)-ketals (IIIa-b). These ketals are mesylated witn methanesulfonyl chloride in pyridine yielding the mesyl ester (IVa-b), which is treated with sodium acetate in DMF to afford the oestradiene ketal (Va-b). Finally, this compound is treated with ethynylmagnesium bromide (B) and refluxed with oxalic acid (C) in methanol.
| 【1】 Hofmeister, H.; Wiechert, R.; Annen, K.; Laurent, H.; Steinbeck, H.; Steroids and pharmaceutical compositions thereof. BE 0847090; FR 2326927; GB 1569135; JP 52046060; US 4081537 . |
| 【2】 Castaner, J.; Blancafort, P.; Gestodene. Drugs Fut 1977, 2, 12, 805. |
| 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) | 12641 | Neopentyl glycol; 2,2-Dimethyl-1,3-propanediol | 126-30-7 | C5H12O2 | 详情 | 详情 |
| (B) | 17778 | ETHYNYLMAGNESIUM BROMIDE; bromo(ethynyl)magnesium | 4301-14-8 | C2HBrMg | 详情 | 详情 |
| (IIIa) | 33952 | C24H36O4 | 详情 | 详情 | ||
| (IIIb) | 33953 | C24H36O4 | 详情 | 详情 | ||
| (IVa) | 33954 | C27H42O4S | 详情 | 详情 | ||
| (IVb) | 33955 | C27H42O4S | 详情 | 详情 | ||
| (Va) | 33956 | C24H34O3 | 详情 | 详情 | ||
| (Vb) | 33957 | C24H34O3 | 详情 | 详情 | ||
| (I) | 33950 | (8R,9S,10R,13S,14S)-13-ethyl-7,8,9,10,11,12,13,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17(2H,6H)-dione | C19H26O2 | 详情 | 详情 | |
| (II) | 33951 | (8R,9S,10R,13S,14S,15S)-13-ethyl-15-hydroxy-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 | |
| (C) | 15713 | Oxalic acid | 144-62-7 | C2H2O4 | 详情 | 详情 |
合成路线2
Ketals (IIIa-b) can also be treated with trimethylsilyl chloride in pyridine to give the trimethylsilyl derivative (VIa-b), which is then treated with ethynylmagnesium bromide (B) and oxalic acid (C) in methanol.
| 【1】 Hofmeister, H.; Wiechert, R.; Annen, K.; Laurent, H.; Steinbeck, H.; Steroids and pharmaceutical compositions thereof. BE 0847090; FR 2326927; GB 1569135; JP 52046060; US 4081537 . |
| 【2】 Castaner, J.; Blancafort, P.; Gestodene. Drugs Fut 1977, 2, 12, 805. |
合成路线3
Ketals (IIIa-b) can also be acetylated with acetic anhydride in pyridine to the acetate (VIIa-b), which is then treated with ethynylmagnesium bromide (B) and oxalic acid (C) in methanol.
| 【1】 Hofmeister, H.; Wiechert, R.; Annen, K.; Laurent, H.; Steinbeck, H.; Steroids and pharmaceutical compositions thereof. BE 0847090; FR 2326927; GB 1569135; JP 52046060; US 4081537 . |
| 【2】 Castaner, J.; Blancafort, P.; Gestodene. Drugs Fut 1977, 2, 12, 805. |