Bioinspired Synthesis of (–)‐Hunterine A: Deciphering the Key Step in the Biogenetic Pathway

A concise, 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 complex structure is an interim-template directed 6-exo selective epoxide ring-opening reaction, which is interwoven with a hydrolysis step of the indolenine hemiaminal template to create the unusual 7-membered azepine bridge motif. Our work not only refines the previously proposed biogenetic pathway, but also reveals the possible stereochemical prerequisite of the unique skeletal rearrangement, which provides a vantage point for understanding how (-)-hunterine A is likely to be generated in nature.