Total Synthesis of Bipolamine I

Abstract

Indolizidine alkaloids have been the target of chemical and biological studies for decades, most recently highlighted by the isolation of the curvulamine and bipolamine polypyrrole-containing subclass. Herein we report a stereoselective 15-step synthesis of bipolamine I, a distinct member of the broader family, and through this work develop an intermediate that will serve to access other polypyrrole natural products and key analogues going forward.

Chemical Investigations of Differentially Oxidized Polycylic Pyrroles from Bipolaris Fungi: Synthetic Entry Into the Bipolamine Alkaloids

“…While the initial stages of biosynthesis have been explored for simple C 10 members (e.g 2 and 3 ), [4] the enzymology underpinning the construction of complex 20‐carbon members (see 1 , 4 – 10 ) remains mysterious. In 2020 we reported the first and only synthetic route to 1 , [5] and very recently, Qiu and Pierce described an elegant total synthesis of bipolamine I ( 10 ) [6] . Herein we report total syntheses of bipolamines D, E, G, and I from a common bispyrrole core now accessible in gram quantities.…”