Title
Structure units oriented approach towards collective synthesis of sarpagine-ajmaline-koumine type alkaloids
Author
Wen Chen, Yonghui Ma, Wenyan He, Yinxia Wu, Yuancheng Huang, Yipeng Zhang, Hongchang Tian, Kai Wei, Xiaodong Yang & Hongbin Zhang
Year
2022
Journal
Nature Communications
Abstract
Sarpagine-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.
Full Article
Instrument
P-2000
Keywords
yttria-magnesia, YM,