Total Synthesis of the Oxopolyene Macrolide (-)-Marinisporolide C

Abstract

The first total synthesis of (-)-marinisporolide C was performed in 25 steps (longest linear sequence) and an overall yield of 1%. Due to the high degree of convergence and robustness, the C9-C35 fragment that corresponds to the polyol portion was obtained in gram quantity. Highlights of this synthesis include five highly stereoselective aldol reactions responsible for the construction of five C-C bonds and six stereogenic centers. Additionally, a very efficient Julia-Kocieński reaction was used to install a C22-C23 double bond, and the macrocyclic ring was closed using an intramolecular Horner-Wadsworth-Emmons olefination.