抗癌药物盐酸吉西他滨合成工艺改进_徐小娇.pdfVIP

广 东 化 工 2012 年 第1 期 · 12 · 第39 卷 总第225 期 抗癌药物盐酸吉西他滨合成工艺改进 1 2 1* 徐小娇 ，杨军 ，邓鹏飞  (1 ．海南师范大学 化学与化工学院 海南省热带药用植物化学重点实验室，海南 海口 571158 ； 2 ．上虞颖泰精细化工有限公司，浙江 上虞 312369) [摘 要]盐酸吉西他滨是一种核苷类抗代谢抗癌药物。笔者利用 2-脱氧-2,2-二氟-D-赤型-呋喃戊糖-1-酮-3,5-二苯甲酸酯经四氢锂铝还原，对 甲苯磺酰氯酯化，与胞嘧啶缩合，甲醇钠脱保护，成盐后重结晶得盐酸吉西他滨。在对甲苯磺酰氯酯化反应进行改进，改用无水碳酸钾作缚酸 剂，降低毒害，经济环保，适合工业化生产。 [关键词]盐酸吉西他滨；抗癌；合成 [中图分类号]TQ [文献标识码]A [文章编号]1007-1865(2012)01-0012-01 Improvement of Synthetic Process of the Anti-cancer Drug of Gemcitabine Hydrochloride 1 2 1* Xu Xiaojiao , Yang Jun , Deng Pengfei (1. Key Lab of Tropical Pharmaceutical Herb Chemistry of Hainan Province, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158 ；2. Shangyu Yingtai Fine Chemical Industry Co., Ltd., Shangyu 312369, China) Abstract: Gemcitabine hydrochloride was an anti-metabolic and anti-cancer nucleoside drug. A method to pro-duce gemcitabine hydrochloride was developed from 2-deoxy-2,2-difluoro-D-erythro-pentofuranose-1-ketose-3,5–di-benzoate via LiAlH4 reduction, p-toluensulfonyl chloride esterification, condensation with cytosine, sodium methox-ide deprotection, salt formation and crystallization. The reaction of p-toluensulfonyl chloride esterification used anh-ydrous potassium. The improvement reduces toxic, and was economic and environmental, suitable for industrial produ-ction. Keywords: gemcitabine hydrochloride ；anti-cance