An Iminium Ion Cascade Annulation Strategy for the Synthesis of Akuammiline Alkaloid Pentacyclic Core Structures

The akuammiline alkaloids are a family of indole monoterpene natural products known for their polycyclic cage-like structures. An iminium ion cascade annulation approach was developed, simultaneously synthesizing both the C and D rings of these natural products by annulation onto a protected indole ring. This reaction allowed the synthesis of a key tetracyclic intermediate toward these natural products. This tetracycle was used for the synthesis of the pentacyclic methano­quinolizidine core present in such alkaloids as akuammiline and strictamine as well as the pentacyclic furoindoline core found in pseudo­akuammigine.