Total Synthesis of Manzamine Alkaloids

Abstract

Manzamine alkaloids are a diverse and highly complex family of marine natural products. The unique macrocyclic structural features of these alkaloids inspired the development of many fascinating synthetic routes. However, the existing strategies typically target only individual alkaloids. Herein we present a detailed insight into a unified approach for the total synthesis of four complex manzamine alkaloids – namely nakadomarin A, manzamine A, ircinal A, and ircinol A – and towards keramaphidin B. The successful synthetic campaign over the past decade is based on stereoselective Michael nitro olefin addition, nitro-Mannich/lactamization cascade, iminium ion/cyclization, stereoselective ring-closing metathesis, and cross-coupling reactions. The development of new catalytic systems for the Michael addition and ring-closing metathesis and unique, powerful route-shortening methodologies has been fundamental for the efficiency of the completed total syntheses.Graphical AbstractOpen image in new window