米非司酮17-位立体异构体的合成及绝对构型确定  

Synthesis and Absolute Configuration Determination of 17-Stereoisomer of Mifepristone

作　　者：靳龙龙 张雅军[1] 孙会敏[1] 路勇[1] 吴先富[1] JIN Longlong;ZHANG Yajun;SUN Huimin;LU Yong;WU Xianfu(National Institutes for Food and Drug Control,Beijing 102629)

机构地区：[1]中国食品药品检定研究院,北京102629

出　　处：《中国医药工业杂志》2022年第12期1715-1718,共4页Chinese Journal of Pharmaceuticals

摘　　要：为了更好地控制米非司酮(1)原料药的质量,设计合成了其17-位立体异构体即11β-[4-(N,N-二甲胺基)-1-苯基]-17α-羟基-17β-(1-丙炔基)-雌甾-4,9-二烯-3-酮(1’)。以1为原料,经发烟硝酸酯化得到17-位硝酸酯,然后在硝酸银存在下水解并发生手性翻转得到1’,产物纯度大于95%。同时,利用电子圆二色谱确证其绝对构型为(8S,11R,13S,14S,17R)。In order to perform the quality control of mifepristone(1),its 17-stereoisomer,11β-[4-(N,Ndimethylamino)-1-phenyl]-17α-hydroxy-17β-(1-propinyl)-estra-4,9-dien-3-one(1’),was synthesized.The target product 1’was prepared from easily available 1 via esterification with fuming nitric acid,hydrolysis and inversion of configuration in the presence of AgNO_(3),with a purity of more than 95%.Meanwhile,its absolute configuration(8S,11R,13S,14S,17R)was determined by electronic circular dichroism.

关 键 词：米非司酮 17-位立体异构体 合成 电子圆二色谱 绝对构型 有关物质 

分 类 号：O626[理学—有机化学]