摘要
目的合成抗癌药盐酸吉西他滨并优化其合成工艺。方法以2-脱氧-2,2-二氟-D-赤式-呋喃戊糖-1-酮-3,5-二苯甲酸酯为起始原料,经还原、甲磺酰化、缩合、脱保护成盐、纯化得到目标化合物盐酸吉西他滨。结果与结论经四步反应和一步纯化过程制得盐酸吉西他滨,其结构经1H-NMR、13C-NMR、MS和IR谱确证。改进后的工艺操作简单,总收率达到7.36%,产品纯度达到99.91%,适合于工业化生产。
Gemcitabine hydrochloride, a nucleoside homologues, was developed by Eli Lilly and Company. It is the only one first-line drug to treat pancreatic cancer. In this paper, a new synthetic route has been estab lished based on the literatures. Using 2-deoxy-2,2-difluoro-D-erythropentofuranos-l-ulose-3,5-dibenzoate as the starting material, gemcitabine hydrochloride was synthesized through five steps, including reduction, mesylation, condensation, deprotection and purification. In the first step, 2-deoxy-2,2-difluoro-D-erythro-ri bofluranose-3,5-dibenzoate （3） was obtained by reduction of the starting material（2） in the presence of Li- A1 （OBu-t）3H in ethyl acetate which acted as both a reaction solvent and extraction solvent. The target com- pound, gemcitabine hydrochloride, was successfully obtained by deprotection of 2＇-deoxy-3＇, 5 ＇-di-O-benzo- yl-2＇ ,2＇-difluorocytidine（5） in the presence of tert-butylamine in methanol. The product was obtained by purified with a mixture solution of water and ethanol. The total yield of the procedure is 7.36% and the pu rity of the final product is 99. 91%. Its structure was confirmed by 1H-NMR, 13C-NMR,IR and MS spectra. The improved process has several advantages over these reported procedures, such as mild conditions and simple operations. Anyway it＇s more suitable for industrial production.
出处
《中国药物化学杂志》
CAS
CSCD
2014年第1期27-30,共4页
Chinese Journal of Medicinal Chemistry
基金
国家十二五"重大新药创制"科技重大专项(2011ZX09203-002-04)
关键词
盐酸吉西他滨
化学合成
抗肿瘤药物
gemcitabine hydrochloride
chemical synthesis
antitumor drug
