Cyclopentanoid natural products display a wide variety of biological activities, and exhibit diverse and complicated architectures. Total synthesis provides the most efficient vehicle for the examination of these molecules' biological effects. Access to natural products and natural product-like compounds also offers a powerful tool for the elucidation and study of the affected biochemical pathways. Chloriolins B and C are highly oxygenated, chlorinated, linearly fused triquinane natural products recently isolated from an unidentified fungus taken from the Indo-Pacific sponge Jaspis aff. johnstoni. This proposal describes the enantioselective total synthesis of these novel molecules. The proposed synthesis involves the development of the asymmetric trimethylenemethane cycloaddition with activated olefins, and its use in establishing the cis-fused BC ring system. A proposed diastereoselective [3+2] cycloaddition will construct the A ring, and will set the stereochemistry at the AB ring fusion. Successful completion of the total synthesis will constitute the first total synthesis of Chloriolins B and C. This project will also introduce a new method for the asymmetric enantioselective synthesis of five-membered rings and demonstrate its usefulness in complex molecule synthesis.
