Epostane, Win-32729
Chemical Name: (2alpha,4alpha,5alpha,17beta)-4,5-Epoxy-17-hydroxy-4,17-dimethyl-3-oxoandrostane-2-carbonitrile
CAS No. 71507-79-4
项目整合开发状态: Phase III
项目研究机构: Sanofi-Aventis (Originator)
合成路线: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.
📌 参考资料/链接：
参考文献标题:Steroid cyanoketones and intermediates
文献作者:Christiansen,R.G.(Sanofi-Synthabo)
参考来源:US 4160027
📄 详细内容
合成路线: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.
参考文献标题:WIN-32,729
文献作者:Castar,J.; Hillier,K.; Blancafort,P.; Serradell,M.N.
参考来源:Drugs Fut 1982,7(9),661
产品链接: CAS No. 71507-79-4››