Bioinspired Synthesis of (–)-Hunterine A: Deciphering a Unique Deconstructive Route

A short, bioinspired, and enantioselective synthesis of (–)- hunterine A, an odd 6/7/6/6/5 pentacyclic natural product, is described. The key step in the synthesis of this daunting structure is the 6-exo selective epoxide ring-opening reaction, which is interwoven with a deconstructive step of the indolenine part to create the unusual 7-membered azepine bridge motif. Our work also reveals the possible mechanism and stereochemical prerequisite of this unique skeletal rearrangement, which provides a vantage point for understanding how (–)-hunterine A is likely to be generated in nature.