替勃龙的合成工艺改进  

Studies on Synthesis of Tibolone

作　　者：邓霞飞[1] 冯长根[1] 张同斌 郑承刚 杨艳青 

机构地区：[1]北京理工大学新医药开发研究中心,北京100081 [2]湖北葛店人福药业有限责任公司,湖北鄂州436070

出　　处：《中国药学杂志》2006年第16期1274-1275,1280,共3页Chinese Pharmaceutical Journal

摘　　要：目的研究替勃龙的合成工艺。方法以3-甲氧基-7α-甲基雌甾-1,3,5(10)-三烯-17β-羟基为起始原料经锂胺还原、草酸水解、缩酮化得3,3-二甲氧基-7α-甲基雌甾-5(10)-烯-17β-羟基(化合物4),然后用温和的氧化剂重铬酸吡啶盐氧化、炔化、再水解得目的产物。结果与结论该合成路线得到替勃龙,总收率较高,为48.3%。替勃龙产品经红外、核磁及质谱证实。OBJECTIVE To study the synthetic process for tibolone. METHODS 3-methoxy-7α-methylestra-1,3,5（10）-trien-17β-ol was reducted with lithium and ammonia, then the intennediate was hydrolyzed in oxalic acid and reacted with malonic acid to get 3, 3- dimethoxo-7α-methylestra-5（ 10）-en-17-ol（compound 4）, which was oxidated by pyridium bichromate, reacted with acetylene, and hydrolyzed in oxalic acid again to get the product tibolone. RESULTS AND CONCLUSION This new synthetic route was successful to get the product tibolone and the overall yield was 48.3% which is higher than reported yield. The stmcture of tibolone was verified by IR, ^1 H-NMR and MS.

关 键 词：替勃龙 合成 温和氧化 重铬酸吡啶盐 

分 类 号：TQ460.6[化学工程—制药化工]