石杉碱甲及其类似物吡啶稠合手性双环[3.3.1]壬烷骨架的不对称构建

doi:10.6023/cjoc202105059

有机化学 ›› 2021, Vol. 41 ›› Issue (10): 4021-4027.DOI: 10.6023/cjoc202105059 上一篇下一篇

所属专题：南开大学化学学科创立100周年；热点论文虚拟合集

研究论文

石杉碱甲及其类似物吡啶稠合手性双环[3.3.1]壬烷骨架的不对称构建

宾怀玉, 程立, 杨小会, 谢建华^*(), 周其林

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:2021-05-31 修回日期:2021-07-07 发布日期:2021-07-19
通讯作者: 谢建华
基金资助:
国家自然科学基金(21871152); 国家自然科学基金(92056105); 国家自然科学基金(21532003); 国家自然科学基金(21790332)

Enantioselective Construction of the Pyridine-Fused Chiral Bicyclo- [3.3.1]nonane Skeleton of Huperzine A and Its Analogues

Huaiyu Bin, Li Cheng, Xiaohui Yang, Jianhua Xie(), Qilin Zhou

State Key Laboratory and Institute of Elemento-organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071

Received:2021-05-31 Revised:2021-07-07 Published:2021-07-19
Contact: Jianhua Xie
Supported by:
National Natural Science Foundation of China(21871152); National Natural Science Foundation of China(92056105); National Natural Science Foundation of China(21532003); National Natural Science Foundation of China(21790332)

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摘要/Abstract

报道了一种不对称构建石杉碱甲及其类似物吡啶稠合手性双环[3.3.1]壬烷骨架的策略. 该策略主要通过具有环外双键的γ,δ-不饱和β-酮酸酯的动态动力学拆分不对称催化氢化, 并结合分子内芳基化反应为关键步骤来不对称构建吡啶稠合手性双环[3.3.1]壬烷骨架. 依据此策略, 从已知的原料出发, 经5步反应以17.4%的总收率完成了石杉碱甲及其类似物核心手性骨架结构的简洁、快速不对称构建.

关键词: 芳基化反应, 不对称催化氢化, 双环[3.3.1]壬烷骨架, 石杉碱甲, 不饱和酮酸酯

A concise strategy for the enantioselective construction of the pyridine-fused chiral bicyclo[3.3.1]nonane skeleton of (+)-huperzine A and its nanlogues was reported. The key features of this strategy are the catalytic asymmetric hydrogenation of an exocyclic γ,δ-unsaturated β-ketoester via dynamic kinetic resolution combined with an intramolecular arylation as the key steps to constuct the pyridine-fused chiral bicyclo[3.3.1]nonane skeleton. This strategy provides a concise and rapid approach to the chiral core structure of huperzine A and its nanlogues from the known starting materials (5 steps and 17.4% overall yield).

Key words: arylation, asymmetric hydrogenation, bicyclo[3.3.1]nonane skeleton, huperzine A, unsaturated ketoester

引用此文

宾怀玉, 程立, 杨小会, 谢建华, 周其林. 石杉碱甲及其类似物吡啶稠合手性双环[3.3.1]壬烷骨架的不对称构建[J]. 有机化学, 2021, 41(10): 4021-4027.

Huaiyu Bin, Li Cheng, Xiaohui Yang, Jianhua Xie, Qilin Zhou. Enantioselective Construction of the Pyridine-Fused Chiral Bicyclo- [3.3.1]nonane Skeleton of Huperzine A and Its Analogues[J]. Chinese Journal of Organic Chemistry, 2021, 41(10): 4021-4027.

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图/表 5

图1. 石杉碱甲及其类似物的结构

Figure 1. Structures of huperzine A and its analogues

图式1. 不对称构建石杉碱甲吡啶稠合手性双环[3.3.1]壬烷骨架的代表性策略

Scheme 1. Representative strategies for enantioselective construction of pyridine-fused chiral bicyclo[3.3.1]nonane skeleton of huperzine A

图式2. 石杉碱甲及其类似物吡啶稠合手性双环[3.3.1]壬烷骨架不对称构建的逆合成分析

Scheme 2. Retrosynthetic analysis of enantioselective construction of the pyridine-fused chiral bicyclo[3.3.1]nonane skeleton of huperzine A and analogues

图式3. 不饱和环状β-羟基酯(+)-3的不对称合成及其催化氢化

Scheme 3. Enantioselective synthesis of unsaturated cyclic β-hydoxy ester (+)-3 and its catalytic hydrogenation

图式4. 酮酸酯(+)-1的不对称合成

Scheme 4. Enantioselective synthesis of ketoester (+)-1

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石杉碱甲及其类似物吡啶稠合手性双环[3.3.1]壬烷骨架的不对称构建

Enantioselective Construction of the Pyridine-Fused Chiral Bicyclo- [3.3.1]nonane Skeleton of Huperzine A and Its Analogues

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