UBC Theses and Dissertations

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UBC Theses and Dissertations

Development of oxidative methodologies and application toward tetrodotoxin core Mendelsohn, Brian Alan


This thesis covers a novel approach to tetrodotoxin that relies on the oxidative amidation of a phenol and intramolecular nitrile oxide cycloaddition to install a β-hydroxynitrile unit among the key steps. These transformations, and others contained herein, effectively set the tetrasubstituted C-8a stereocenter, as well C-4a formyl equivalent and C-5, C-7 and C-8 hydroxyl groups. Novel reaction types were developed in the course of this work, including a new method for the oxidation of oximes to nitrile oxides using hypervalent iodine reagents. Additionally, I identified a tandem reaction sequence, involving the dearomatization of a phenol, followed by [3+2]-dipolarcycloaddition, the first of its kind. This tandem sequence proved a powerful tool for the rapid construction of multicyclic compounds from structurally simpler starting materials. These studies resulted in advanced intermediates which contained much of the structure of the tetrodotoxin core.

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