有机化学 ›› 2015, Vol. 35 ›› Issue (6): 1353-1356.DOI: 10.6023/cjoc201412036 上一篇    下一篇

研究简报

氯化两面针碱合成方法的改进

许旭升a,b, 刘志千b, 邵文浩b, 叶霁b, 孙青龑b, 何薇薇a, 张卫东a,b   

  1. a 华东理工大学药学院 上海 200237;
    b 第二军医大学药学院 上海 200433
  • 收稿日期:2014-12-20 修回日期:2015-01-28 出版日期:2015-06-25 发布日期:2015-02-10
  • 通讯作者: 张卫东 E-mail:heweiwei@ecust.edu.cn
  • 基金资助:

    国家自然科学基金(81230090)、上海市重点学科建设(No. B906)资助项目.

Process Improvement on the Synthesis of Nitidine Chloride

Xu Xushenga,b, Liu Zhiqianb, Shao Wenhaob, Ye Jib, Sun Qingyanb, He Weiweia, Zhang Weidonga,b   

  1. a College of Pharmacy, East China University of Science and Technology, Shanghai 200237;
    b College of Pharmacy, The Second Military Medical University, Shanghai 200433
  • Received:2014-12-20 Revised:2015-01-28 Online:2015-06-25 Published:2015-02-10
  • Supported by:

    Project supported by the NSFC (No. 81230090), the Shanghai Leading Academic Discipline Project (No. B906).

以6-溴-3,4-二甲氧基苯甲醛和6,7-亚甲二氧基-1-萘胺为起始原料, 经还原胺化、分子内Heck偶联、氧化芳构化、甲基化以及离子交换等五步反应, 完成了氯化两面针碱的合成, 并对关键步骤分子内Heck偶联反应条件进行了探索, 结果表明该偶联反应在醋酸钯、三(邻甲苯基)膦和N,N'-二甲基甲酰胺体系中反应效果最佳, 收率显著提高. 该优化条件为结构类似苯并[c]菲啶类生物碱母核结构的构建提供了借鉴.

关键词: 氯化两面针碱, 分子内Heck偶联反应, 合成改进

Nitidine chloride was synthesized via reductive amination, intramolecular Heck coupling reaction, aromatization, methlyation and ion exchange, using 6-bromine-3,4-dimethoxybenzaldehyde and 6,7-methylenedioy-1-naphthylamine as starting material. The key intramolecular Heck coupling reaction was optimized, and acetic acid palladium(II) [Pd(OAc)2], tris(2-methylphenyl)phosphine [P(o-tol)3] and N,N-dimethylformamide (DMF) system was confirmed as the most efficient conditions. The total yield was increased significantly, and the optimal conditions may also be applied to the synthesis of other benzo[c]phenanthridine alkaloid.

Key words: nitidine chloride, intramolecular Heck reaction, synthesis