Advances in the Total Synthesis of Dihydrolycolucine

Abstract

Dihydrolycolucine is a Lycopodium alkaloid that has gained attention over the recent years due to its complex architecture and potential medicinal value. In an effort to synthesize this alkaloid, multiple approaches were envisioned to arrive at the key tetracyclic northern zone. Each approach was centered upon an intramolecular Diels-Alder and retro-Mannich ring-opening sequence to deliver the cis-perhydroquinoline ring system which underwent subsequent manipulation for the installment of the appropriate pyridine motif. Closure of the seven-membered ring utilizing palladium enolate chemistry was examined in detail. Further examination has revealed that ring closure may also be affected via the use of N-acylpyridinium salt chemistry and progress toward this methodology will be described herein.