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【结 构 式】 
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【药物名称】Dienogest, MJR-35, M-18575, STS-557, Climodien(comb. with estradiol valerate), Klimodien(comb. with estradiol valerate), Valette(comb. with ethinyl estradiol), Endometrion 【化学名称】17alpha-Cyanomethyl-17beta-hydroxy-13beta-methylgona-4,9-dien-3-one 【CA登记号】65928-58-7 【 分 子 式 】C20H25NO2 【 分 子 量 】311.42775 |
【开发单位】Jenapharm (Originator), Schering AG (Originator), Innothera (Licensee), Mochida (Licensee) 【药理作用】Contraceptives, Disorders of Sexual Function and Reproduction, Treatment of, ENDOCRINE DRUGS, Endometriosis Therapy, Female Contraceptives, Gynecological Disorders, Treatment of , Hormone Replacement Therapy, Oral Contraceptives, Progestogens |
合成路线1
The bromination of 17-alpha-cyanomethyl-17-beta-hydroxy-13-beta-methylgona-5(10)-ene-3-one (I) with polyvinylpyridinium bromide perbromide yields dibromide (II), which immediately debrominates to the final product.
| 【1】 Huebner, M.; Menzenbach, B. (Akademie der Wissenschaften der DDR); Verfahren zur herstellung von steroiden mit einem 4,9-diensystem. DD 205170 . |
| 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) | 29717 | 2-[(8R,13S,14S,17R)-17-hydroxy-13-methyl-3-oxo-2,3,4,6,7,8,9,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]acetonitrile | C20H27NO2 | 详情 | 详情 | |
| (II) | 29718 | 2-[(8S,13S,14S,17R)-5,10-dibromo-17-hydroxy-13-methyl-3-oxohexadecahydro-1H-cyclopenta[a]phenanthren-17-yl]acetonitrile | C20H27Br2NO2 | 详情 | 详情 |
合成路线2
1,4-Dihydroestronemethylether (I) was reacted with dimethylsulfonium-methylide (A) in a highly stereoselective manner to give the oxirane (II), which formed the cyanomethyl compound (III) by the addition of sodium cyanide. (III) was hydrolyzed with oxalic acid (B) in methanol and the product (IV) treated with pyridine perbromide hydrobromide to the dibromoketone, which yielded STS-557 after dehydrobromination.
| 【1】 Cook, C.E.; et al.; Synthesis and reactions of oxiranes obtained from 3- and 17-keto steroids. J Org Chem 1968, 33, 2789. |
| 【2】 Hubner, M.; et al.; Ein vereinfachtes Verfahren zur Darstellung von Steroid-Spirooxiranen. J Prakt Chem 1972, 314, 667. |
| 【3】 Ponsold, K.; et al.; Prostagene vom Typ 17alpha-CH2X-substituierter 19-Nortestossteronderivate. Pharmazie 1978, 33, 792. |
| 【4】 Perelman, M.; et al.; A new class of active steroids: the 19-nor-delta(4,9)-3-ketosteroids. J Am Chem Soc 1960, 82, 2402. |
| 【5】 Unterhalt, B.; STS-557. Drugs Fut 1980, 5, 6, 311. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 15713 | Oxalic acid | 144-62-7 | C2H2O4 | 详情 | 详情 |
| (A) | 16180 | Dimethyl(methylene)-lambda(4)-sulfane; Dimethylsulfonium-methylide | C3H8S | 详情 | 详情 | |
| (I) | 32635 | 1,4-Dihydroestronemethylether; (8R,9S,13S,14S)-3-methoxy-13-methyl-1,4,6,7,8,9,11,12,13,14,15,16-dodecahydro-17H-cyclopenta[a]phenanthren-17-one | C19H26O2 | 详情 | 详情 | |
| (II) | 32637 | 3-Methoxyspiro[estra-2,5(10)-diene-17(S),2'-oxirane] | C20H28O2 | 详情 | 详情 | |
| (III) | 32636 | 2-[(8R,9S,13S,14S,17R)-17-hydroxy-3-methoxy-13-methyl-4,6,7,8,9,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]acetonitrile | C21H29NO2 | 详情 | 详情 | |
| (IV) | 32638 | 2-[(8R,9S,13S,14S,17R)-17-hydroxy-13-methyl-3-oxo-2,3,4,6,7,8,9,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]acetonitrile | C20H27NO2 | 详情 | 详情 |