The proposal describes the total, non-racemic synthesis of two cytotoxic marine natural products, Asbestinin-6 and Sclerophytin A. The mechanism of cytotoxicity in not understood for either of these compounds, and a hypothesis is given. To help establish the causative motifs present in the metabolites, synthetic studies are proposed. Central to the synthetic proposals, is the development of a novel tetrahydrofuran synthesis that uses a 2-cyanotetrahydrofuran as a nucleophile, potentially effecting medium-ring synthesis. If successful, the total synthesis of the targets would be possible, establishing a convergent route to Eunicellin-based metabolites. Further studies would be aimed at the design of analogues to probe the mechanism of cytotoxicity present in a large number of structurally related metabolites.
