The Friedel–Crafts alkylation is a powerful C–C bond forming reaction used in many industrial chemical processes, coupling aromatic rings and alkyl halides to access compounds relevant for fuels, synthetic rubber, plastics, and detergents. However, this reaction’s utility is limited due to lack of stereo and regiocontrol, the fact that multiple alkylation events are more likely to occur than single ones, and the requirement for strong Lewis acids to activate alkyl halides generates carbocationic intermediates that can undergo unproductive rearrangements. Recently, our group identified CylK, a biosynthetic enzyme from <i>Cylindrospermum licheniforme </i>that catalyzes an analogous C–C bond forming event which – if successfully harnessed as a biocatalyst – could overcome these shortcomings. CylK enables a sequential head-to-tail dimerization of a chlorinated alkyl resorcinol, a key step in the biosynthesis of cylindrocyclophane F. Importantly, this reaction catalyzed by CylK is regiospecific, and it preserves stereochemical information at the chlorinated carbon through an inversion of configuration. Additionally, we have preliminarily demonstrated that CylK is promiscuous for non-native substrates, including alkyl fluorides. We are working to solve a crystal structure of this enzyme and carry out mutagenesis studies in order to characterize how this remarkable chemistry occurs.

Characterization of a cyanobacterial “Friedel–Crafts alkylase” enzyme

256th National Meeting (2018)

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