# Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives

## TL;DR

Scientists found a new way to remove methyl groups from certain chemicals using thiols, avoiding oxygen and achieving high efficiency.

## Contribution

A novel anaerobic biocatalytic demethylation method using thiols as methyl traps is introduced.

## Key findings

- Cobalamin-dependent methyltransferases can demethylate guaiacol derivatives anaerobically using thiols.
- A wide range of substituted guaiacol derivatives were demethylated with over 90% conversion.
- Hydroxytyrosol was produced on a one-gram scale with 97% isolated yield.

## Abstract

Demethylating methyl phenyl ethers is challenging, especially when the products are catechol derivatives prone to follow‐up reactions. For biocatalytic demethylation, monooxygenases have previously been described requiring molecular oxygen which may cause oxidative side reactions. Here we show that such compounds can be demethylated anaerobically by using cobalamin‐dependent methyltransferases exploiting thiols like ethyl 3‐mercaptopropionate as a methyl trap. Using just two equivalents of this reagent, a broad spectrum of substituted guaiacol derivatives were demethylated, with conversions mostly above 90 %. This strategy was used to prepare the highly valuable antioxidant hydroxytyrosol on a one‐gram scale in 97 % isolated yield.