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Formal total synthesis of (±)-tetrodotoxin

University of British Columbia

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.

Text

2016-10-19

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/59489

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/