(S)-(–)-Xylopinine和(S)-(+)-Laudanosine的不对称合成
收稿日期: 2023-04-25
修回日期: 2023-05-19
网络出版日期: 2023-05-25
基金资助
广东省教育厅基金(2021KCXTD044)
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
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 . DOI: 10.6023/cjoc202304032
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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