抗癌药物多烯紫杉醇的合成  

Synthesis of anticancer drug docetaxel

作　　者：景临林[1] 金瑛[1] 张生勇[1] 孙晓莉[1] 

机构地区：[1]第四军医大学药学系化学教研室,陕西西安710032

出　　处：《中国药物化学杂志》2006年第5期292-295,共4页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(50372084)

摘　　要：目的建立一种简便、经济的合成多烯紫杉醇的方法。方法以反式-肉桂酸乙酯为原料,经不对称双羟化、环氧化、重氮化及氢化4步反应得到多烯紫杉醇手性C13侧链,再与保护的10-去乙酰巴卡亭Ⅲ对接、去保护得到多烯紫杉醇。结果多烯紫杉醇手性C13侧链的4步反应总收率为76%,光学产率为99%,对接及去保护3步反应总收率为64%。结论在多烯紫杉醇手性C13侧链的合成过程中,对价格昂贵的金鸡纳生物碱衍生物配体进行了回收和再利用,大大降低了反应成本。同时还优化了反应过程,避免了柱色谱分离,有利于多烯紫杉醇的工业化生产。Aim To develop a simple and economical method to synthesize docetaxel. Methods With transethyl cinnamate as starting material, chiral docetaxel C13 side chain was synthesized through asymmetric dihydroxylation（AD）, epoxidation, diazotization and hydrogeneration. Then it was coupled with protected baccatin Ⅲ, followed by deprotection to afford docetaxel. Results Chiral docetaxel Cl3 side chain was synthesized in 76 % yield and 99 % ee. The total yield of coupling and deprotecting reaction was 64 %. Conclusion In the synthetic procedure to chiral docetaxel Cl3 side chain, the expensive cinchona alkaloid derivatives can be recycled, which dramatically decreased the reaction cost. Meanwhile, the synthetic route is simplified by avoiding chromatograph and might be benefit for industrialization.

关 键 词：药物化学 药物制备 化学合成 可回收配体 多烯紫杉醇C13侧链 多烯紫杉醇 

分 类 号：R914[医药卫生—药物化学]