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

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–Kocienski reaction was used to install a C22–C23 double bond, and the macrocyclic ring was closed using an intramolecular Horner–Wadsworth–Emmons olefination.