# Biocatalytic Regioselective C‐Formylation of Resorcinol Derivatives

## TL;DR

Scientists discovered a new enzyme that can efficiently and selectively add formyl groups to resorcinol derivatives, a process that was previously not possible with biocatalysts.

## Contribution

The discovery of a biocatalytic method for regioselective C-formylation of resorcinol derivatives using CsATase.

## Key findings

- CsATase enables regioselective C-formylation of resorcinol derivatives with up to 99% conversion and 74% yield.
- CsATase outperforms chemical methods in formylation of phloroglucinol, yielding di-formylated products.
- X-ray crystallography revealed structural insights into the active site of CsATase.

## Abstract

Although aromatic formylation reactions are highly valuable from a synthetic perspective, a biocatalytic version has not yet been reported. Here, the cofactor‐independent multimeric three‐component acyltransferase from Chromobacterium sphagni (CsATase) was identified to enable the nonnatural promiscuous regioselective C‐formylation of polyphenolic substrates, especially resorcinol derivatives, and thus extending the reaction scope of acyltransferases. Formylation of 4‐ and 5‐substituted resorcinol derivatives gave access to regioselectively mono‐formylated products with up to 99% conversion and up to 74% isolated yield. Formylation of phloroglucinol led to the di‐formylated product with 99% conversion, outperforming chemical methods. Structural analysis of CsATase by X‐ray crystallography provided insights into its active site.

An acyltransferase from Chromobacterium sphagni (CsATase) was identified that catalyzes the regioselective formylation of resorcinol substrates. The formylation of substituted resorcinol derivatives yielded mono‐formylated products with up to 99% conversion and up to 74% isolated yield. The structure of CsATase was elucidated by X‐ray crystallography, providing insight into its active site.