Oxidative dearomatization is a powerful transformation, however, a limited number of highly enantioselective catalytic methods have been reported. Nature performs this reaction catalytically with excellent site- and stereoselectivity under mild conditions. For example, direct hydroxylation is performed seamlessly by the flavin-dependent monooxygenase TropB. This enzyme can achieve complete conversion of phenol substrates to dearomatized products in 1 h using molecular oxygen as the stoichiometric oxidant. TropB-catalyzed hydroxylation provides an efficient route to chiral intermediates valuable for the synthesis of complex bioactive molecules without the drawbacks of conventional chemical methods. To expand the substrate scope of TropB, a structure-guided protein engineering effort was employed. Overall, these efforts have enhanced the synthetic utility of this biocatalyst. Structural information has also informed a set of mechanistic hypotheses, which have been probed through mutagenesis experiments.

Expanding the synthetic utility of the Flavin-dependent monooxygenase TropB

256th National Meeting (2018)

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