石蒜碱(+)-β-、(+)-γ-和(-)-δ-Lycorane的全合成研究

	石蒜碱(+)-β-、(+)-γ-和(-)-δ-Lycorane的全合成研究
	张泸月
导师	杨玉荣
关键词	石蒜碱，铱/胺双元催化，烯丙基烷基化，不对称全合成 Lycorane, Iridium/amine dual catalysis, Allylic alkylation, Asymmetric total synthesis
摘要	石蒜科生物碱lycorane具有三个连续手性中心以及独特的吡咯并菲啶四环结构。而且还有丰富的药理活性，受到了国内外许多有机合成化学家的关注。本论文主要论述了石蒜科生物碱中(+)-β-lycorane、(+)-γ-lycorane和(-)-δ-lycorane基于Carreira铱/胺双元催化不对称烯丙基化的全合成研究，包含以下两章内容。第一章初步介绍了石蒜碱的构型分类以及药理活性，并简要综述了国内外β-lycorane、γ-lycorane和δ-lycorane的代表性全合成研究工作。第二章主要概述了我们课题组对石蒜碱(+)-β-lycorane、(+)-γ-lycorane和(-)-δ-lycorane的不对称全合成研究。从简单易得的烯丙基二级醇和醛基化合物出发，由关键的Carreira铱/胺双元催化不对称烯丙基化反应，一次性构建出lycorane两个连续手性中心，并通过手性诱导或不对称氢化等途径构建出第三个手性中心。接着通过烯烃复分解、Mitsunobu和Bischler-Napieralski环化等反应完成lycorane母核的构建，最终可以快速实现(+)-β-lycorane、(+)-γ-lycorane和(-)-δ-lycorane的不对称全合成。该项研究工作中所采用立体发散式合成策略，可进一步应用在更多石蒜科生物碱的全合成中。; Lycorane, an alkaloid of the family Amaryllidaceae, has three consecutive chiral centers and a unique tetracyclic pyrrolophenanthridine structure. Moreover, it has rich pharmacological activities, which has attracted the attention of many organic synthetic chemists at home and abroad. This thesis focuses on iridium-catalyzed asymmetric allylation total syntheses of Amaryllidaceae alkaloids (+)-β-lycorane, (+)-γ-lycorane and (-)-δ-lycorane, including the following two chapters. The first chapter preliminarily introduced the configuration classification and pharmacological activities of lycorine, and briefly reviewed the representative total synthesis of β-lycorane, δ-lycorane and γ-lycorane at home and abroad. The second chapter mainly summarizes the asymmetric total synthesis of lycorine (+)-β-lycorane, (+)-γ-lycorane and (-)-δ-lycorane by our group. Starting from simple and readily available allylic secondary alcohols and aldehyde-based compounds, the key Carreira iridium/amine binary catalyzed asymmetric allylation reaction constructs two consecutive chiral centers of lycorane at one time. The third chiral center is constructed by induction or asymmetric hydrogenation. Then, the lycorane core is constructed by alkene metathesis, Mitsunobu reaction and Bischler-Napieralski cyclization. Finally, the asymmetric total synthesis of (+)-β-lycorane, (+)-γ-lycorane and (-)-δ-lycorane can be realized rapidly. The stereo-divergent synthesis strategy adopted in this research work can be further applied to the total synthesis of more Amaryllidaceae alkaloids.
语种	中文
	2022-05
学位授予单位	中国科学院大学
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75104
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	张泸月. 石蒜碱(+)-β-、(+)-γ-和(-)-δ-Lycorane的全合成研究[D]. 中国科学院大学,2022.

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