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Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361964/ https://www.ncbi.nlm.nih.gov/pubmed/34057803 http://dx.doi.org/10.1002/anie.202104278 |
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author | Pompei, Simona Grimm, Christopher Schiller, Christine Schober, Lukas Kroutil, Wolfgang |
author_facet | Pompei, Simona Grimm, Christopher Schiller, Christine Schober, Lukas Kroutil, Wolfgang |
author_sort | Pompei, Simona |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8361964 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83619642021-08-17 Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives Pompei, Simona Grimm, Christopher Schiller, Christine Schober, Lukas Kroutil, Wolfgang Angew Chem Int Ed Engl Communications 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. John Wiley and Sons Inc. 2021-06-29 2021-07-26 /pmc/articles/PMC8361964/ /pubmed/34057803 http://dx.doi.org/10.1002/anie.202104278 Text en © 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Communications Pompei, Simona Grimm, Christopher Schiller, Christine Schober, Lukas Kroutil, Wolfgang Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives |
title | Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives |
title_full | Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives |
title_fullStr | Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives |
title_full_unstemmed | Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives |
title_short | Thiols Act as Methyl Traps in the Biocatalytic Demethylation of Guaiacol Derivatives |
title_sort | thiols act as methyl traps in the biocatalytic demethylation of guaiacol derivatives |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8361964/ https://www.ncbi.nlm.nih.gov/pubmed/34057803 http://dx.doi.org/10.1002/anie.202104278 |
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