Asymmetric Total Synthesis of Tetrodotoxin

The research described in this proposal will provide access to tetrodotoxin, a potent neurotoxin widely used in pharmacological studies as a probe for sodium channels. This highly complex molecule will be assembled in optically pure form in a concise manner using a novel synthetic strategy. Furthermore, the proposed synthetic route is flexible enough to permit preparation of natural congeners of tetrodotoxin as well as its nonnatural analogs. The structure-activity relationship study of these derivatives, which cannot be accessed by chemical modification of tetrodotoxin itself, will make possible a better understanding of the structure and the mechanism of action of the sodium channel.