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

Asymmetric Synthesis of (S)-(–)-Xylopinine and (S)-(+)-Laudanosine

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.

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.