Synthesis of Bis-Strychnos Alkaloids (–)-Sungucine, (–)-Isosungucine, and (–)-Strychnogucine B from (–)-Strychnine

It was developed a concise synthetic route resulting in the first syntheses of bis-Strychnos alkaloids (-)-sungucine, (-)-isosungucine, and (-)-strychnogucine B from commercially available (-)-strychnine. Employing a highly convergent synthetic strategy, it was demonstrated that both Strychnos monomers could be efficiently prepared from commercially available (-)-strychnine. The venerable Mannich reaction was enlisted to join the two Strychnos monomers in a biomimetic fashion. Subsequent epimerization and olefin isomerization yielded (-)-strychnogucine B. Functional group manipulation transformed (-)-strychnogucine B into (-)-sungucine and (-)-isosungucine. Computational chemistry was employed to rationalize the regiochemical course of key steps en route to the bis-Strychnos targets.

本研究开发了一条简洁合成路线，首次以商业化可得的(-)-马钱子碱（(-)-strychnine）为起始原料，完成了双马钱子生物碱（bis-Strychnos alkaloids）类化合物(-)-sungucine、(-)-isosungucine与(-)-strychnogucine B的全合成。研究采用高度汇聚式合成策略，证实可通过商业化易得的(-)-马钱子碱高效制备构成该类双生物碱的两种马钱子单体（Strychnos monomers）；借助经典曼尼希反应（Mannich reaction）以仿生路径实现两单体的偶联，后续经差向异构化与烯烃异构化反应得到(-)-strychnogucine B，再通过官能团修饰将其转化为(-)-sungucine与(-)-isosungucine。此外，本研究采用计算化学手段，阐明了双马钱子生物碱靶标合成路径中关键步骤的区域选择性历程。