醋酸乌利司他的合成  

Synthesis of Ulipristal Acetate

作　　者：刘庆庆[1] 余永国[1] 海俐[1] 郭丽[1] 吴勇[1] 

机构地区：[1]四川大学华西药学院,四川成都610041

出　　处：《中国医药工业杂志》2015年第3期233-237,共5页Chinese Journal of Pharmaceuticals

摘　　要：3,3-(亚乙二氧基)雌甾-5(10),9(11)-二烯-17-酮经乙炔加成,与苯硫氯反应,脱苯亚磺酰基,去甲基重排,羰基保护制得3,3:20,20-二(亚乙二氧基)-17α-羟基-19-去甲孕甾-5(10),9(11)-二烯(7),7以六氟丙酮为催化剂环氧化制得3,3:20,20-二(亚乙二氧基)-17α-羟基-5α,10α-环氧-19-去甲孕甾-9(11)-烯,然后经格氏加成、去保护、乙酰化合成醋酸乌利司他,总收率23.1%,纯度99.8%。优化后工艺生产成本低,生产周期短,操作简便。Ulipristal acetate was synthesized from 3,3- （ethylenedioxy） estra-5 （10） ,9 （11） -diene- 17-one via acetylene addition, reaction with benzenesulfenyl chloride, debenzenesulfinyl reaction, rearrangement, carbonyl-protection to give 3,3：20,20-bis （ethylenedioxy）-17α-hydroxy-19-norpregn-5 （10）,9 （11）-diene （7）, followed by epoxidation with hexafluoroacetone as catalyst to obtain 3,3：20,20-bis （ethylenedioxy）-17α-hydroxy-5α,10α-epoxy-19-norpregn-9 （11）- ene, which was subjected to Grignard addition, deprotection and acetylation with an overall yield of 23.1% and an HPLC purity of 99.8%. The optimized process had several advantages, such as low cost, short production period and simple operations.

关 键 词：醋酸乌利司他 合成 工艺 纯化 

分 类 号：R979.21[医药卫生—药品]