有机化学 ›› 2020, Vol. 40 ›› Issue (11): 3963-3968.DOI: 10.6023/cjoc202007052 上一篇    下一篇

研究简报

(-)-吲哚里西啶167B和(+)-毒芹碱的不对称合成

杨小会, 顾雪松, 宾怀玉, 谢建华, 周其林   

  1. 南开大学化学学院 元素有机化学国家重点实验室 天津 300071
  • 收稿日期:2020-07-22 修回日期:2020-07-29 发布日期:2020-08-11
  • 通讯作者: 谢建华, 周其林 E-mail:jhxie@nankai.edu.cn;qlzhou@nankai.edu.cn
  • 基金资助:
    国家自然科学基金(No.21532003,21871152,21790332)资助项目.

Asymmetric Synthesis of (-)-Indolizidine167B and (+)-Coniine

Yang Xiaohui, Gu Xuesong, Bin Huaiyu, Xie Jianhua, Zhou Qilin   

  1. a State Key Laboratory and Institute of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071
  • Received:2020-07-22 Revised:2020-07-29 Published:2020-08-11
  • Supported by:
    Project supported by the National Natural Science Foundation of China (Nos. 21532003, 21871152, 21790332).

报道了基于消旋δ-羟基酯的动力学拆分不对称催化氢化不对称合成(-)-吲哚里西啶167B和(+)-毒芹碱.用消旋5-羟基辛酸乙酯经手性螺环铱催化剂Ir-(R)-SpiroPAP不对称氢化得到的光学活性δ-羟基酯(S)-4和1,5-二醇(R)-5为手性原料,建立了分别以分子内还原胺化和胺基取代环化反应为关键步骤构建手性氮杂[4.3.0]壬烷骨架和手性哌啶环的合成方法,完成了(-)-吲哚里西啶167B和(+)-毒芹碱的高效不对称合成.这为吲哚里西啶和哌啶类生物碱的不对称合成提供了新的有效方法.

关键词: 生物碱, 不对称氢化, 吲哚里西啶, 毒芹碱, 还原胺化

The enantioselective syntheses of (-)-indolizidine 167B and (+)-coniine were described based on the asymmetric hydrogenation of racemic δ-hydroxy esters via kinetic resolution. With optically active chiral δ-hydroxy ester (S)-4 and chiral 1,5-diol (R)-5 obtained by asymmetric hydrogenation of racemic ethyl 5-hydroxyoctanoate (rac-4) with chiral spiro iridium catalyst Ir-(R)-SpiroPAP as chiral starting materials, the efficient enantioselective syntheses of (-)-indolizidine 167B and (+)-coniine were achieved by using intramolecular reductive amination and N-substitution/cyclization, respectively, as a key step to construct the chiral aza-bicyclic[4.3.0]nonane skeleton and chiral piperidine ring. This provides new efficient methods for enantioselective syntheses of indolizidine and piperidine alkaloids.

Key words: alkaloids, asymmetric hydrogenation, indolizidine, coniine, reductive amination