State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Tianshui Road 222, Lanzhou, 730000, Gansu, P. R. China.
Angew Chem Int Ed Engl. 2022 Aug 8;61(32):e202205439. doi: 10.1002/anie.202205439. Epub 2022 Jun 21.
It is reported herein that by exploiting the commonly shared bicyclic decahydroquinoline motif, a gold-catalyzed enamide-alkyne cycloisomerization reaction is developed to access tricyclic cores in a simple way. These tricyclic cores further serve as an advanced platform for the divergent enantioselective collective total syntheses of five Lycopodium alkaloids, belonging to three different structural types, in a concise and protecting-group-free fashion. The key transformations in the second phase include: 1) a transannular reductive Heck cyclization for installation of the azepane ring in fawcettidine, fawcettimine, and lycoposerramine Q; 2) a domino Mukaiyama hydration/Grob fragmentation process for construction of the ten-membered lactam system in phlegmariurine B; 3) a Fukuyama one-pot protocol for the construction of the 2-pyridone motif in lycoposerramine R. The newly developed strategy is expected to pave the way for the synthesis of other structurally related Lycopodium alkaloids.
本文报道了一种金催化的酰胺-炔环异构化反应，通过利用普遍存在的双环十氢喹啉结构基序，以简单的方式构建三环核心。这些三环核心进一步作为一个先进的平台，用于以简洁、无保护基的方式对属于三种不同结构类型的五种石松生物碱进行发散对映选择性的集体全合成。第二阶段的关键转化包括：1）反环还原 Heck 环化反应，用于在 fawcettidine、fawcettimine 和 lycoposerramine Q 中安装氮杂环庚烷环；2）Mukaiyama 缩合/Grob 断裂反应的串联反应，用于在 phlegmariurine B 中构建十元内酯系统；3）Fukuyama 一锅法反应，用于在 lycoposerramine R 中构建 2-吡啶酮结构。新开发的策略有望为其他结构相关的石松生物碱的合成铺平道路。
