Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 60, Issue 31, Pages 16906-16910Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202104278
Keywords
biotransformation; cobalamin-dependent enzymes; demethylation; methyl phenyl ethers; thioethers
Categories
Funding
- Austrian Science fund [P30920-B21]
- University of Graz
- Field of Excellence BioHealth
- Austrian Science Fund (FWF) [P30920] Funding Source: Austrian Science Fund (FWF)
Ask authors/readers for more resources
This study demonstrates that demethylating methyl phenyl ethers can be achieved anaerobically using cobalamin-dependent methyltransferases exploiting thiols as a methyl trap. This strategy allows for efficient and high-yielding synthesis of the antioxidant hydroxytyrosol.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available