Epoxyquinol A is a heterodimeric epoxyquinoid natural product that has demonstrated inhibitory activity in the nuclear factor-κB pathway, a property identified as being important for the study and treatment of a broad range of disease states (e.g. cancer, autoimmune disorders). Two approaches to the total synthesis of this representative epoxyquinoid will be presented. In both cases the application of a benzoate dihydroxylation reaction, using benzoate-1-2- dioxygenase (BZDO) expressed in Ralstonia eutropha B9 whole cells, will be highlighted. The obtained (1S,2R)-1,2-dihydroxycyclohexa-3,5-diene-1-carboxylic acids provide chiral building blocks from which to pursue asymmetric synthesis of epoxyquinol A. The first approach relies on an orthogonal protection strategy to allow selective epoxidation of the diene system and to facilitate an oxidative transposition of a tertiary alcohol to form the enone core. Completion of a formal synthesis of epoxyquinol A via this route will be described. The second approach, which seeks to install the desired epoxide though an iodolactonization reaction, will also be presented. The selectivity of this reaction and conversion of obtained iodolactones into core structures suitable for epoxyquinoid synthesis will be discussed.

Chemoenzymatic approaches to the total synthesis of epoxyquinol A

2019 Spring National Meeting

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