原料药左炔诺孕酮有关物质的制备研究  

Study on Preparation of the Related Substances of Levonorgestrel

作　　者：蒋婷 刘喜荣 孙昊星 刘艳飞[1] Jiang Ting;Liu Xirong;Sun Haoxing;Liu Yanfei(School of Chemistry and Chemical Engineering,Central South University,Changsha 410083;Hunan Norchem Pharmaceutical Co.,Ltd.,Changsha 410001,China)

机构地区：[1]中南大学化学化工学院,湖南长沙410083 [2]湖南新合新生物医药有限公司,湖南长沙410001

出　　处：《广东化工》2021年第16期39-40,68,共3页Guangdong Chemical Industry

基　　金：中南大学研究生自主探索创新项目(2020zzts409);长沙市科技计划项目(kq2004086)。

摘　　要：目的:制备欧洲药典中原料药左炔诺孕酮有关物质的杂质Ⅰ。方法:以17α-乙炔基-17β-羟基-18-甲基-3-甲氧基-甾-2,5(10)二烯(SM1)为原料,经水解、环氧化和环氧开环等反应,或以左炔诺孕酮(SM2)为原料,经缩酮化、环氧化、环氧开环等反应,得到目标产物17α-乙炔基-10β,17β-二羟基-18-甲基-甾-4-烯-3-酮。结果与结论:采用核磁和质谱对最终产物进行了结构确证,两条反应路线均可成功合成左炔诺孕酮有关物质的杂质I,以SM1为原料反应产率较高,总收率为30%,以SM2为原料反应产率总收率为19%。Objective: To synthesis the impurity I of related substance in levonorgestrel, which was reported by European Pharmacopoeia. Method: The target product 17α-Ethynyl-10 β, 17β-dihydroxy-18-methylgon-4-ene-3-one was obtained from 17α-Ethynyl-17β-hydroxy-18-methyl-3-methoxygon-2, 5(10)-diene(SM1) by hydrolysis, epoxidation and epoxide ring-opening reactions, or from levonorgestrel(SM2) by ketalization, epoxidation and epoxide ring-opening reactions. Results and conclusion: The structure of the final product was confirmed by NMR and MS, the target product can be successfully synthesized by the two reaction routes, the reaction yield with SM1 as raw material is higher, the total yield of SM1 used as raw material was 30 %, and that of SM2 used as raw material was 19 %.

关 键 词：左炔诺孕酮 有关物质 杂质Ⅰ 合成 结构确证 

分 类 号：O62[理学—有机化学]