抗癌药盐酸吉西他滨的合成工艺研究

Synthesis of gemcitabine hydrochloride

S-甘油醛缩丙酮经Reformasty反应、脱异丙叉基保护、内酯化及双苯甲酰化得到2-脱氧-2,2-二氟-D-赤型-呋喃戊糖-1-酮-3,5-二苯甲酸酯,再经四氢铝锂还原、甲磺酰化、缩合得2-脱氧-2',2'-二氟胞苷-3',5'-二苯甲酸酯,然后经脱保护基,成盐后经丙酮-水体系重结晶分离得盐酸吉西他滨,总收率6.2%。

3,5-Di-O-benzoyl-2-deoxy-2,2-difluoro-D-ribose was prepared from （S）-glyceraldehyde acetonide via successively Reformasty reaction, deprotect, lactonization and benzoylation. The resulting intermediate was converted to 2 ＇-deoxy-2 ＇ , 2 ＇-difluoro-3 ＇ , 5 ＇-di-O-benzoyl-cytidine via reduction with LiA1H4, methylsulfonation and condensation. Then protect group was removed and the crude product salt was obtained in HC1. After a crystallization in aqueous acetone, the final product was got with an overall yield of 6.2%.