高等学校化学学报 ›› 2012, Vol. 33 ›› Issue (03): 511.doi: 10.3969/j.issn.0251-0790.2012.03.015

• 有机化学 • 上一篇    下一篇

5,8-二取代吲哚里西丁毒青蛙生物碱的合成

周德军1,2, 丰岗尚树2   

  1. 1. 河南理工大学物理化学学院, 焦作 454000;
    2. 富山大学药学部, 日本富山 930-0194
  • 收稿日期:2011-04-19 出版日期:2012-03-10 发布日期:2012-03-10
  • 通讯作者: 周德军, 男, 博士, 讲师, 主要从事药物化学研究. E-mail:zhoudj@hpu.edu.cn
  • 基金资助:

    河南理工大学博士启动基金资助.

Syntheses of 5,8-Disubstituted Indolizidine Poison-frog Alkaloids

ZHOU De-Jun1,2, TOYOOKA Naoki2   

  1. 1. Department of Chemistry, School of Physics and Chemistry, Henan Polytechnic University, Jiaozuo 454000, China;
    2. Faculty of Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
  • Received:2011-04-19 Online:2012-03-10 Published:2012-03-10

摘要:

建立了一种以Michael共轭加成为关键步骤, 高立体选择性合成5,8-二取代吲哚里西丁生物碱的方法, 同时对5,8-二取代吲哚里西丁毒青蛙生物碱(-)-203A, (-)-209B, (-)-235B″, (-)-231C, (-)-233D, (-)-219F, (-)-221I, (-)-193E(Proposed), (-)-251N和221K(Proposed)进行了全合成, 确定了203A和233D的绝对构型及231C, 219F, 221I和251N的相对构型. 另外, 对193E(Proposed)的结构提出了订正方案.

关键词: Michael共轭加成, 毒青蛙生物碱, 全合成, 绝对构型, 相对构型

Abstract:

A diverse array of biologically active alkaloids has been detected in amphibian skin, which contains over 20 structural classes and more than 800 alkaloids. Most of these alkaloids appear to be derived from dietary sources such as ants, beetles, mites and so on. A great number of the alkaloids show very interesting biological activities such as pharmacological effects at neuronal nicotinic acetylcholine receptors. However, these alkaloids have been isolated in minute amounts from the amphibian skin. Consequently, a great need for the development of the synthetic strategy of these alkaloids has arisen for the determination of the structures of natural products and the investigations of their biological activities. The 5,8-disubstituted indolizidines constitute the largest subclass of alkaloids, and about 80 alkaloids have been detected up to present. In this paper, we report the syntheses of the analogous indolizidines (-)-203A, (-)-209B, (-)-235B″, (-)-231C, (-)-233D, (-)-219F, (-)-221I, (-)-193E(Proposed), (-)-251N and 221K(Proposed) using the stereoselective Michael conjugate addition reaction as the key step. Furthermore, the absolute stereochemistry of (-)-203A and (-)-233D was established, and the relative stereochemistry of 231C, 219F, 221I and 251N was established.

Key words: Michael conjugate addition, Poison-frog alkaloid, Total synthesis, Absolute stereochemistry, Relative stereochemistry

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