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有机化学
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有机化学 ›› 2015, Vol. 35 ›› Issue (5): 1161-1165.DOI: 10.6023/cjoc201410026 上一篇    下一篇

研究简报

抗癌药物达卡巴嗪的合成工艺优化

肖胜伟a, 刘志军a, 柳杨a, 陈河如a,b   

  1. a 暨南大学药学院中药及天然药物研究所 广州 510632;
    b 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
  • 收稿日期:2014-10-18 修回日期:2014-12-19 发布日期:2015-01-07
  • 通讯作者: 陈河如 E-mail:thrchen@jnu.edu.cn
  • 基金资助:

    国家自然科学基金(No.81172982)资助项目.

Optimization of the Synthetic Process of Antineoplastic Drug Dacarbazine

Xiao Shengweia, Liu Zhijuna, Liu Yanga, Chen Herua,b   

  1. a Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632;
    b Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632
  • Received:2014-10-18 Revised:2014-12-19 Published:2015-01-07
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No.81172982).

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补充材料

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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.

关键词: 达卡巴嗪, 工艺优化, 药物合成, 抗癌

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 charac-terized by applied cheap materials, mild conditions, and good overall yield.

Key words: dacarbazine, process optimization, drug synthesis, anticancer