17β-羟基-4ɑ,5ɑ-环氧雄甾烷并[2,3-d]异噁唑的合成工艺改进  

Improved Synthesis of 4ɑ,5ɑ-Epoxy-androst-2-eno[2,3-d]isoxzol-17β-ol

作　　者：李永[1] 朱桃[1] 樊玲玲[1] 王建塔[1] 汤磊[1] 

机构地区：[1]贵阳医学院,贵州贵阳550004

出　　处：《中国医药工业杂志》2015年第4期346-348,共3页Chinese Journal of Pharmaceuticals

基　　金：贵州省高等学校创新能力提升计划(黔教合协同创新字[2013]04)

摘　　要：17β-羟基雄甾-4-烯-3-酮与甲酸乙酯在甲醇钠条件下经缩合生成17β-羟基-2-羟亚甲基雄甾-4-烯-3-酮,与盐酸羟胺环合形成17β-羟基-4-烯-雄甾烷并[2,3-d]异噁唑,最后经m-CPBA环氧化制得曲洛司坦关键中间体17β-羟基-4ɑ,5ɑ-环氧雄甾烷并[2,3-d]异噁唑,总收率为70%,纯度为99.1%。4ɑ,5ɑ-Epoxy-androst-2-eno[2,3-d]isoxzol-17β-ol, the key intermediate of trilostane, was synthesized from 17β-hydroxy-4-androsten-3-one by condensation with ethyl formate in the presence of sodium methoxide to give 2-hydroxymethylene-androst-4-en-3-one-17β-ol, which was subjected to cyclization with hydroxylamine hydrochloride to afford androst-4-eno[2,3-d]isoxazol-17β-ol, followed by epoxidation with m-CPBA with an overall yield of 70% and purity of 99.1%.

关 键 词：17β-羟基-4ɑ 5ɑ-环氧雄甾烷并[2 3-d]异噁唑 曲洛司坦 库欣综合征 原发性醛固酮增多症 中间体 合成 

分 类 号：R979.9[医药卫生—药品] O629[医药卫生—药学]