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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...

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Autores principales: Pompei, Simona, Grimm, Christopher, Schiller, Christine, Schober, Lukas, Kroutil, Wolfgang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
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.
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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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