DESCRIPTION: This grant application describes a program directed toward the total synthesis of brevetoxin A (I) and maitotoxin (III). These target molecules are potent neurotoxins associated with massive marine life and food poisoning, and they are expected to provide opportunities for discovery and invention in the areas of chemical synthesis and chemical biology. Specifically, a number of new synthetic reactions and strategies will be developed and several model systems, advanced intermediates and designed biological mimics will be synthesized and tested. The significance of the proposed work lies in chemical synthesis and biomedical research, as well as protection of the marine environment and seafood resources.