Biaryl bonds are prevalent in a vast array of drug molecules and natural product scaffolds. These biaryl frameworks have applications in asymmetric catalysis, medicine and material science. Traditionally, these compounds are synthesized using metal-catalyzed cross-coupling reactions. These reactions can present a challenge in achieving high levels of reactivity and selectivity for a given set of substrates, including atroposelectivity, chemoselectivity, and site-selectivity. To overcome the issues associated with this transformation, a biocatalytic approach towards biaryl bond formation is proposed. Nature has evolved cytochrome P450 enzymes (P450s), to mediate the oxidative dimerization of these compounds in the biosynthesis of biaryl natural products.<br/><br/>This work highlights two main projects relating to the development of biocatalytic oxidative biaryl bond-forming reactions. First, the development of a library of previously uncharacterized P450 enzymes into tunable biocatalysts for convergent oxidative cross-coupling reactions with catalyst-controlled reactivity, site-selectivity, and atroposelectivity. Second, the exploration of these enzymes for unnatural dimerization and cross-coupling reactions. A high throughput platform was leveraged to investigate the scope and reactivity of the P450 library against a panel of diverse molecular scaffolds. These biocatalysts allow the synthesis of many complex biaryl molecules giving access to the molecular frameworks of natural products with known therapeutic potential.

Development of biocatalytic oxidative cross-coupling reactions for the formation of biaryl bonds

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