Total Synthesis of (+)-Alstonlarsine A: Old Reactions in Modern Alkaloids Synthesis

Abstract

(+)-Alstonlarsine A is a recently isolated monoterpenoid indole alkaloid, possessing a novel pentacyclic skeleton and interesting biological activity, making it an attractive target for synthetic chemists. In this article we focus on its total synthesis, grounded on enamine formation/Diels-Alder reaction domino sequence, as well as a novel methodology for indole C(2) functionalization via carbenoid insertion, which could also allow for the synthesis of other indole alkaloids possessing cycloalka[b]indole subunits.

Intramolecular Dearomative Inverse-Electron-Demand Diels Alder Strategy for the Total Synthesis of (+)-Alstonlarsine A

“…Due to its uniquely intricate and intriguing architecture associated with a specific bioactivity, alstonlarsine A ( 1 ) attracted considerable attention of scientific community. This culminated in two orthogonal enantioselective syntheses of (+)-alstonlarsine A ( 1 ) published almost simultaneously by Zhai and our group in 2022, while shortly after a proposedly biomimetic conversion of Strychnos type alkaloids alstolucines B and F into alstonlarsine A ( 1 ) demonstrated its putative biogenetic origin (Scheme ). Herein, we present a full account of our work, showing in details how the final synthetic route evolved from the initial approaches.…”