Synthetic Studies on Halichlorine and Pinnaic Acid. Stereospecific Preparation of the Azaspiro Core Structure

Abstract

Halichlorine and pinnaic acid are two novel marine natural products isolated from a Japanese sponge and an Okinawan bivalve, respectively. The unique azaspiro[4.5]decane core structure present in both compounds provides a synthetic challenge. Herein, we describe a synthetic approach to the azaspiro[4.5]decane core structure through an intramolecular [3 + 2] cycloaddition followed by an intramolecular Michael addition and in situ isomerization to afford the azaspirocyclic core structures stereospecifically in 10 steps with 40% overall yield.