Towards the total synthesis of gambieric acid A

Abstract

Over the past three decades, numerous polycyclic ether natural products have been isolated from marine organisms. All of these unusual compounds possess a wide range of biological activities. In 1992, a new family of polyethers was discovered from the marine dinoflagellate Gambierdiscus toxicus: gambieric acids A–D, which show antifungal activity against a variety of filamentous fungi. The purpose of this thesis is to show the progress towards the synthesis of F–J ring system of gambieric acid A. First, the large scale synthesis of I–G ring fragment using the two directional ring closing metathesis developed in the laboratory is described including the improvements made to the previous synthesis. Subsequently, the efficient introduction of the methyl group of the F ring using a 1,4 addition with a cuprate reagent to an a,b-unsaturated lactone is discussed in detail. In addition, efficient introduction of the side chain to the J ring using a cyclic siloxane using a model system is also reported, after the exploration of ten different approaches. Finally, studies concerning the final stages of the synthesis are discussed