抗癌药物达卡巴嗪的合成工艺优化  

Optimization of the Synthetic Process of Antineoplastic Drug Dacarbazine

作　　者：肖胜伟[1] 刘志军[1] 柳杨[1] 陈河如[1,2] 

机构地区：[1]暨南大学药学院中药及天然药物研究所,广州510632 [2]广东省中药药效物质基础及创新药物研究重点实验室,广州510632

出　　处：《有机化学》2015年第5期1161-1165,共5页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.81172982)资助项目~~

摘　　要：以廉价易得的甘氨酸为原料,经酯化、甲酰化、脱水、酰氨化得到异氰基乙酰胺,四步总收率42.9%.异氰基乙酰胺与氨基腈在碱性条件下环合得到重要中间体5-氨基-4-咪唑甲酰胺,收率68.2%.随后经重氮化,与二甲胺偶联,得最终产物达卡巴嗪,总收率22.3%.所有中间体以及目标产物的结构均由1H NMR,13C NMR和ESI-MS确证.合成路线具有原料廉价、反应条件温和、总收率较高等特点,是一条经济实用的合成工艺路线.Dacarbazine has been prepared started from glycine, which was carried on firstly through a four-step process including esterification, formylation, dehydration, amidation to give 2-isocyanoacetamide with a total yield of 42.9%. 2- Isocyanoacetamide was then cyclized with cyanamide under basic condition to afford the important intermediate 5-amino-1H-imidazole-4-carboxamide with yield of 68.2%. This intermediate undergoing diazotization and following coupling reaction with dimethylamine led to the target compound. The overall yield was 22.3%. All the intermediates and the target products dacarbazine were confirmed by ^1H NMR, ^13C NMR and ESI-MS. The current process is economic efficient characterized by applied cheap materials, mild conditions, and good overall yield.

关 键 词：达卡巴嗪 工艺优化 药物合成 抗癌 

分 类 号：TQ463[化学工程—制药化工]