Lara, Zentsche, Jessica, Yazarians, Suman, Chakrabarty, Meagan, Hinze, April, Lukowski, Leo, Joyce and Alison, Narayan (2022) Biaryl bond formation through biocatalytic oxidative cross-coupling reactions. Nature, 603. pp. 79-85. ISSN https://doi.org/10.1038/s41586-021-04365-7

Abstract

Biocatalysis offers compelling advantages in synthesis, often becoming the method of choice
based on sustainability, safety, and selectivity considerations. Despite these advantages, enzymes in
synthesis are typically dedicated to functional group interconversions in linear synthetic sequences and
have not been broadly integrated into the retrosynthetic logic for carbon skeleton assembly. In this article,
we disclose a biocatalytic platform for fragment coupling to assemble target molecules convergently.
Specifically, we report a strategy for biocatalytic phenolic cross-coupling through oxidative C–C bond
formation. Using cytochrome P450 enzymes, we demonstrate the ability to catalyze cross-coupling
reactions on a panel of phenolic substrates and further demonstrate the ability to tune these catalysts to
possess the desired reactivity, site-, and atroposelectivity. This streamlined method for constructing
sterically-hindered biaryl bonds provides an engineerable platform for assembling molecules with
programmable catalyst-controlled reactivity and selectivity unprecedented with small molecule catalysts

Item Type:	Article
Date Deposited:	10 May 2022 00:45
Last Modified:	10 May 2022 00:45
URI:	https://oak.novartis.com/id/eprint/45267