In Nature, complex molecules are often built through reactive intermediates that allow access to diverse structures. Traditional chemical methods to access these fleeting intermediates can require blocking groups and often possess limited functional group tolerance. Our lab recently developed a method for biocatalytically initiated ortho-quinone methide formation and diversification using non-heme iron oxygenases. Substrates with an o-cresol core can be enzymatically converted to benzylic alcohols which, upon mild heating, are transformed into o-quinone methide intermediates that can be captured with nucleophiles or dienophiles, thereby generating new C–O, C–N, C–S, and C–C bonds. To find enzymes capable of benzylic hydroxylation on a diverse set of substrates, we built a library of non-heme iron oxygenases, whose sequences came directly from Nature. We anticipate this library and chemoenzymatic o-quinone methide approach will allow for the synthesis of several biologically active natural products.

Chemoenzymatic total synthesis enabled by sampling non-heme iron enzyme sequence space

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.