Formal total synthesis of (±)-tetrodotoxin

This dissertation details a formal total synthesis of (±)-tetrodotoxin, a potent sodium channel blocker, based on a transformation developed in these laboratories: the bimolecular oxidative amidation of phenols. The present route leads to the Du Bois intermediate in 27 steps from a commercial starting material. Because the Du Bois intermediate can be elaborated to tetrodotoxin in 4 steps, this work constitutes a formal synthesis of the natural product in 31 steps. This is competitive with the best known alternatives. A structural revision of the Sato tetrodotoxin intermediate is also provided. Finally, an even more concise avenue to a new bis-lactonic precursor of the natural product is described, and potential enantioselective routes to tetrodotoxin are discussed.Science, Faculty ofChemistry, Department ofGraduat