Synthetic Studies toward Madeirolide A

Abstract

Madeirolide A is isolated from the marine sponge Leiodermatium sp., and has been shown to be a potent growth inhibitor of Candida albicans, a pathogenic fungus. Madeirolide A has a complicated structure with a 24-membered macrolactone and 16 stereocenters. The bioactivity and structural complexity make madeirolide A an attractive target for total synthesis. Our approach for the synthesis of madeirolide A is based on the assembly of four fragments – C1-C10 fragment (A ring), C11-C19 fragment (B ring), C20-C27 fragment (C ring), and cinerulose fragments. Using a free radical-mediated reductive cyclization method developed from our group, three oxacycles in the compound have been envisioned to be efficiently created under novel photoredox catalysis of an iridium complex. Described in this thesis are the synthetic studies of the three fragments of madeirolide A.