We present studies toward the total synthesis of madeirolide A. This compound has been isolated from the marine sponge Leiodermatium sp., and has been shown to be a potent 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 synthesis is based on the assembly of four fragments. Using reductive cyclization developed from our group, three oxacycles in the compound have been envisioned to be efficiently created under novel photoredox catalysis of an iridium complex. Here we describe the introduction of the synthesis of the C1-C10 part of madeirolide A.