利用替柯吉宁合成地塞米松  

SYNTHESIS OF DEXAMETHASONE FROM TIGOGENIN

作　　者：马如鸿 费得青[1] 游晓燕 应瑞芬[1] 卞恩培 张丽青[2] 

机构地区：[1]上海医药工业研究院 [2]中国科学院有机化学研究所

出　　处：《中国医药工业杂志》1989年第1期1-5,共5页Chinese Journal of Pharmaceuticals

摘　　要：利用替柯吉宁为原料,经14步反应制得地塞米松。自2引入16α-甲基-17α-羟基可在氯化亚铜存在下,经甲基溴化镁1,4-加成并直接加入乙酐生成17(20)-烯醇酯,再经环氧化,水解反应完成,收率90％。烯醇酯环氧化物4的一组异构物亦已分离和鉴定。1,4-脱氢可通过化学法或微生物法进行。11β-羟基物(10)可用梨头霉氧化得到。自16α-甲基强的松龙可按常法合成地塞米松。Dexamethasone was synthesized from tigogenin in 14 steps. Theintroduction of 16a-methy-17a-hydroxy into steroid 2 could be achieved by 1,4-addition of Grignard reagent in the presence of CuCl and subsequent acetylationin one port to afford 3 which was subjected to epoxidation and hydrolysis togive 5in90% yield. Among them, two isomers of epoxide 4 were separated andidentified. The 1-and 4-double bonds were introduced by bromination anddehydrobromination followed by dehydrogenation with SeO_2, or by microbialtransformation. Compound 8 was incubated with a mixture of Mycobacteriumsmegmatis and Arthrobacter simplex to give 9. 11-Hydroxylation of 9 by Absidiatransformation gave about 40% of 10. Dexamethasone could further be synthesizedin 5 steps by the usual method.

关 键 词：地塞米松 替柯吉宁 制药工艺 激素 

分 类 号：TQ468.95[化学工程—制药化工]