抗肿瘤药物卡培他滨的合成工艺改进  

Improved synthesis of anticancer drug capecitabine

作　　者：余建鑫[1] 张万年[1] 姚建忠[1] 宋云龙[1] 盛春泉[1] 

机构地区：[1]第二军医大学药学院,上海200433

出　　处：《中国药物化学杂志》2005年第3期173-175,187,共4页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(20302013)

摘　　要：目的改进抗肿瘤药物卡培他滨的合成工艺。方法经酰化保护的D-核糖与硅醚化的5-氟胞嘧啶反应,生成中间产物2′,3′,5′O-三苯甲酰-5-氟胞苷(4),后者经皂化、形成酮缩、碘化、氢解及水解等反应合成了5-氟脱氧胞苷,最后与正戊基氯甲酸酯反应生成卡培他滨。结果以D-核糖为起始原料经8步反应合成卡培他滨。结论改进后的合成方法工艺简便、条件温和、原料易得,总收率由文献方法的12%提高为22%,适于工业制备。Aim To improve the synthetic procedure of the anticancer drug capecitabine.Method 2′,3′,5′-tri-O-benzoyl-5-fluorocytidine(4)was obtained by the reaction of protected D-ribose with trimethylsilylated 5-fluorocytosine.After saponification,ketal formation,iodation,hydrogenolysis and hydrolysis,the intermediate 4 can be reacted with n-pentyl chloroformate to give capecitabine.Result The anticancer drug capecitabine was synthesized by using D-ribose as the starting material in 8 steps.Conclusion The starting material is very easy to get,the reaction conditions are moderate and the operation is convenient.The reaction steps are shortened,and the total yield is increased to 22% from 12% yield of the reference.This method is suitable for industrial producing.

关 键 词：药物化学 工艺改进 化学合成 卡培他滨 抗肿瘤 

分 类 号：TQ463.53[化学工程—制药化工]