(S)-(–)-Xylopinine和(S)-(+)-Laudanosine的不对称合成

doi:10.6023/cjoc202304032

有机化学 ›› 2023, Vol. 43 ›› Issue (9): 3297-3303.DOI: 10.6023/cjoc202304032 上一篇下一篇

(S)-(–)-Xylopinine和(S)-(+)-Laudanosine的不对称合成

张俊杰, 徐学涛^*()

五邑大学生物科技与大健康学院广东江门 529020

收稿日期:2023-04-25 修回日期:2023-05-19 发布日期:2023-05-23
通讯作者: 徐学涛
基金资助:
广东省教育厅基金(2021KCXTD044)

Junjie Zhang, Xuetao Xu()

School of Biotechnology and Health Science, Wuyi University, Jiangmen, Guangdong 529020

Received:2023-04-25 Revised:2023-05-19 Published:2023-05-23
Contact: Xuetao Xu
Supported by:
Department of Education of Guangdong Province(2021KCXTD044)

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摘要/Abstract

四氢原小檗碱家族天然产物具有较好的生物活性, 其中xylopinine具有良好的抗疟疾活性, laudanosine则具有癫痫治疗活性. 报道了一种不对称合成( S)-(–)-xylopinine和( S)-(+)-laudanosine的策略. 该策略主要通过叔丁基亚磺酰亚胺发生非对映选择性1,2-加成, 并结合分子内Pictet-Spengler反应为关键步骤, 完成了四氢原小檗碱的分子骨架构建. 依据此策略, 从已知原料3,4-二甲氧基苯乙酸出发, 经7步反应分别以11.1%和16.4%的总收率完成了( S)-(–)-xylo- pinine和( S)-(+)-laudanosine的简洁、快速不对称合成. 通过对比xylopinine之间的比旋光度和laudanosine之间的比旋光度, 可以证明所合成的两个天然产物C(14)均为 S构型.

关键词: xylopinine, laudanosine, 叔丁基亚磺酰胺, 非对映选择性加成

Tetrahydroprotoberberine alkaloids have good bioactivity against malaria and epilepsy, among them, xylopinine has good anti malaria activity, while laudanosine has epilepsy treatment activity. A concise asymmetric synthesis of ( S)-(–)- xylopinine and ( S)-(+)-laudanosine has been reported. The key strategies include diastereoselective nucleophilic addition to N-tert-butanesulfinimine, which is combined with Pictet-Spengler reaction as a key step for constructing the pivotal tetrahydroprotoberberine skeleton. This strategy provides a concise and rapid approach to ( S)-(–)-xylopinine (7 steps and 11.1% overall yield) and ( S)-(+)-laudanosine (7 steps and 16.4% overall yield) from known starting materials. The S configuration of synthetic xylopinine and laudanosine at C(14) is confirmed by comparing their specific rotation data.

Key words: xylopinine, laudanosine, N-tert-butanesulfinimine, asymmetric addition

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张俊杰, 徐学涛. (S)-(–)-Xylopinine和(S)-(+)-Laudanosine的不对称合成[J]. 有机化学, 2023, 43(9): 3297-3303.

Junjie Zhang, Xuetao Xu. [J]. Chinese Journal of Organic Chemistry, 2023, 43(9): 3297-3303.

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图/表 5

图1. xylopinine和laudanosine的结构

Figure 1. Structures of xylopinine and laudanosine

图式1. 四氢原小檗碱骨架合成的代表性策略

Scheme 1. Representative strategies for construction of tetrahydroprotoberberine skeleton

图式2. Xylopinine和laudanosine的逆合成分析

Scheme 2. Retrosynthetic analysis of xylopinine and laudanosine

图式3. 化合物4和5的合成

Scheme 3. Synthesis of compounds 4 and 5

图式4. Xylopinine (1)和laudanosine (2)的不对称合成

Scheme 4. Enantioselective synthesis of xylopinine (1) and laudanosine (2)

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(S)-(–)-Xylopinine和(S)-(+)-Laudanosine的不对称合成

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