Structure units oriented approach towards collective synthesis of sarpagine-ajmaline-koumine type alkaloids

• DOI: 10.1038/s41467-022-28535-x
• Publication Date: 2022-02-17T11:03:18Z
• Authors: Wen Chen; Yonghui Ma; Wenyan He; Yinxia Wu; Yuancheng Huang; Yipeng Zhang; Hongchang Tian; Kai Wei; Xiaodong Yang; Hongbin Zhang
• Keywords: Ajmaline; Molecular Structure; Cyclization; Science; Q; Stereoisomerism; Chemistry Techniques, Synthetic; 01 natural sciences; Article; Indole Alkaloids; 0104 chemical sciences

AbstractSarpagine-Ajmaline-Koumine type monoterpenoid indole alkaloids represent a fascinating class of natural products with polycyclic and cage-like structures, interesting biological activities, and related biosynthetic origins. Herein we report a unified approach towards the asymmetric synthesis of these three types of alkaloids, leading to a collective synthesis of 14 natural alkaloids. Among them, akuammidine, 19-Z-akuammidine, vincamedine, vincarine, quebrachidine, vincamajine, alstiphylianine J, and dihydrokoumine are accomplished for the first time. Features of our synthesis are a new Mannich-type cyclization to construct the key indole-fused azabicyclo[3.3.1]nonane common intermediate, a SmI2 mediated coupling to fuse the aza-bridged E-ring, stereoselective olefinations to install either the 19-E or 19-Z terminal alkenes presented in the natural alkaloids, and an efficient iodo-induced cyclization to establish the two vicinal all-carbon quaternary centers in the Koumine-type alkaloids.