有机化学 ›› 2013, Vol. 33 ›› Issue (05): 869-876.DOI: 10.6023/cjoc201301035 上一篇    下一篇

研究专题

分子内氧化偶联反应在合成复杂吲哚生物碱骨架中的应用

谢卫青, 左智伟, 资伟伟, 马大为   

  1. 中国科学院上海有机化学研究所 生命有机化学国家重点实验室 上海 200032
  • 收稿日期:2013-01-15 修回日期:2013-01-31 出版日期:2013-05-25 发布日期:2013-02-01
  • 通讯作者: 谢卫青,xiewq@sioc.ac.cn;马大为,madw@sioc.ac.cn E-mail:xiewq@sioc.ac.cn;madw@sioc.ac.cn
  • 基金资助:

    国家重点基础研究发展计划(973计划, No. 2010CB833200)资助项目.

Intramolecular Oxidative Coupling: Applications in Synthesis of Complex Indole Akaloid Scaffolds

Xie Weiqing, Zuo Zhiwei, Zi Weiwei, Ma Dawei   

  1. State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032
  • Received:2013-01-15 Revised:2013-01-31 Online:2013-05-25 Published:2013-02-01
  • Supported by:

    Project supported by the National Basic Research Program of China (973 Program, No. 2010CB833200).

通过含有吲哚底物的分子内氧化偶联反应, 成功地构建了Communesin家族生物碱的螺吲哚啉季碳中心, 从而完成了(-)-Communesins A, B和F的对映选择性合成. 接下来我们发展了分子内氧化偶联/缩合串联反应策略, 得到了天然产物(-)-Vincorine的核心四环骨架, 然后再经过五步转化完成了Vincorine的全合成. 从药物化学角度来看, 分子内氧化偶联/缩合串联提供了一个快速方便地合成含有多环吲哚啉骨架的方法. 采用相同的串联反应策略, 我们分别从色胺衍生的β-酮酸酰胺和丙二酸二酰胺出发, 一步构建了多环螺吲哚啉和多环吲哚啉并吡咯环骨架分子.

关键词: 分子内氧化偶联, 吲哚生物碱, 全合成, 多环螺吲哚啉, 吲哚并吡咯环

Intramolecular oxidative coupling of tryptamine incorporated amide was used to create the quaternary spiroindoline carbon center of communesins, which enabled a short asymmetric synthesis of (-)-communesins A and B and F. The fused tetra-ring framework of Vincorine was established by an intramolecular oxidative coupling/condensative cyclization process, which was further advanced to (-)-vincorine in 5 steps. From a medicinal standpoint, such a cascade process provides a highly diverse, efficient method for the construction of polycyclic spiroindoline scaffolds. Starting from easily accessible tryptamine incorporated β-ketoamides and malonamides, polyclic spiroindolines and pyrroloindolines could be directly obtained by adopting the same cascade strategy.

Key words: intramolecular oxidative coupling, indole alkaloids, total synthesis, polycyclic spiroindoline, pyrroloindoline