卡培他滨的合成工艺研究  

Study on Synthesis Technology of Capecitabine

作　　者：杨建楠[1] 杜有国[1] 宗在伟[1] 唐尧[1] 

机构地区：[1]江苏奥赛康药业有限公司,南京211112

出　　处：《中国药师》2011年第6期796-798,共3页China Pharmacist

摘　　要：目的：改进抗肿瘤药物卡培他滨的合成工艺。方法：5-氟胞嘧啶经硅烷化保护后与1，2，3一三-O-乙酰基-13-D-呋喃核糖缩合反应，得到2，3-二-O-乙酰基-5’-脱氧-5-氟胞苷，后者与氯甲酸正戊酯酰胺化反应后经过甲醇钠／甲醇体系脱保护得到卡培他滨，重点考察了硅烷化保护剂以及不同碱性体系对脱保护反应的影响。结果：采用以上工艺，四步反应合成了卡培他滨并通过^1H-NMR和MS确认。结论：成功改进了卡培他滨的合成工艺，提高了收率，质量可控，适合工业化生产。Objective： To optimize the synthesis procedure of capecitabine. Method： Capecitabine was prepared starting irom 5- fluorocytosine via four steps,including silylation, condensation, acylamination and deprotection. Effects of silyation reagents and reaction temperature on silylation, and alkaline system on hydrolysis had been studied. Result： Capecitabine was synthesized in the route as mentioned above from 5-fluorocytosine and identified by ^1HNMR and ESI-MS. Conclusion： This improved synthesis process has the advantages of shorter synthesis route with higher yield and better quality, which is suitable for industrial production.

关 键 词：卡培他滨 工艺改进 硅烷化保护 水解反应 

分 类 号：R914.5[医药卫生—药物化学]