Chabamide酰胺生物碱的不对称合成

发布时间：2018-04-17 16:11

本文选题：不对称合成 + Michael加成　；参考：《云南大学》2016年硕士论文

【摘要】：Chabamide酰胺生物碱是一个从黑胡椒根中分离出来的酰胺二聚体天然产物分子。活性研究表明该天然产物分子具有较好的抗肿瘤活性及抑制中枢神经系统兴奋作用,所以对Chabamide酰胺生物碱进行不对称合成研究在不对称合成及医药研发领域具有重要意义。在C-C键的构建中,Michael加成反应是一种重要的合成方法。不对称Michael加成反应可以用来构建许多天然有机分子及其中间体和药物分子中的手性中心,且反应条件温和,构建过程高效、简洁同时具有较高的选择性。因此,不对称Michael加成反应目前已经发展成为了最有效的化学键构建方法之一。本文第一章首先对不对称Michael加成反应以及Chabamide酰胺生物碱的研究工作进行了综述性介绍。然后简介了以有机小分子催化的不对称Michael加成反应来构筑该天然产物分子中手性中心六元环的探究,以期能够完成对该分子的不对称合成。在手性六元环的构筑中,文章采用了三种不同的催化模式,分别是基于氢键作用的金鸡纳碱-硫脲催化、基于烯胺作用的金鸡纳碱-伯胺催化以及基于亚胺离子中间体作用的L-脯氨酸-硅醚催化。经过不对称Michael加成反应底物的合成以及不对称催化合成,最终得到了环合的手性六元环中间体16'、18和24。为Chabamide酰胺生物碱的不对称合成打下了基础,同时也为该类天然产物分子类似物的药用研究提供了化合物基础。
[Abstract]:Chabamide amide alkaloid is a natural product molecule of amide dimer isolated from black pepper root.Studies on the activity of the natural product show that the natural product has good antitumor activity and inhibition of central nervous system excitation, so the asymmetric synthesis of Chabamide amide alkaloids is of great significance in the field of asymmetric synthesis and pharmaceutical research and development.Michael addition reaction is an important synthetic method in the construction of C-C bond.Asymmetric Michael addition reaction can be used to construct chiral centers of many natural organic molecules, their intermediates and drug molecules. The reaction conditions are mild, the construction process is efficient, and the process is simple and selective.Therefore, asymmetric Michael addition reaction has been developed as one of the most effective chemical bond construction methods.In the first chapter, the asymmetric Michael addition reaction and the research work of Chabamide amide alkaloids are reviewed.Then the asymmetric Michael addition reaction catalyzed by small organic molecules was briefly introduced to construct the chiral central six-member ring in the natural product molecule in order to complete the asymmetric synthesis of the molecule.In the construction of chiral six-member ring, three different catalytic modes were used in this paper.The catalytic activity of cinchona alkaloid-primary amine based on enamine and L-proline-silica ether catalyst based on the intermediate of imine ion.After the synthesis of asymmetric Michael addition substrates and asymmetric catalytic synthesis, the chiral chiral hexagonal intermediates of 16 ~ (18) and 24 ~ (th) were obtained.It lays a foundation for the asymmetric synthesis of Chabamide amide alkaloids, and also provides the basis for the medicinal research of this kind of natural product molecular analogues.
【学位授予单位】：云南大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：O629.3

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