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

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. The sarpagine-ajmaline-koumine type alkaloids are among the most important groups of monoterpenoid indole alkaloids, having notable biological activity. Here the authors perform divergent syntheses of 14 natural products in this family from a common intermediate.

Automated summary

The authors report a unified approach towards the asymmetric synthesis of Sarpagine-Ajmaline-Koumine type alkaloids, leading to the synthesis of 14 natural alkaloids. These alkaloids have significant biological activities.