Oxygen-Free Regioselective Biocatalytic Demethylation of Methyl-phenyl Ethers via Methyltransfer Employing Veratrol-O-demethylase
| Autor: | Nina Richter, Mattia Lazzarotto, Christopher Grimm, Wolfgang Kroutil, Johanna Schichler, Simona Pompei, Michael Fuchs, Judith E. Farnberger |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
biocatalysis
010405 organic chemistry Aryl methyltransferases fungi ether cleavage Regioselectivity demethylation General Chemistry 010402 general chemistry Cleavage (embryo) 01 natural sciences Medicinal chemistry Catalysis 0104 chemical sciences chemistry.chemical_compound veratrol-O-demethylase chemistry Biotransformation Biocatalysis biotransformation Ether cleavage Demethylation Research Article |
| Zdroj: | ACS Catalysis |
| ISSN: | 2155-5435 |
| Popis: | The cleavage of aryl methyl ethers is a common reaction in chemistry requiring rather harsh conditions; consequently, it is prone to undesired reactions and lacks regioselectivity. Nevertheless, O-demethylation of aryl methyl ethers is a tool to valorize natural and pharmaceutical compounds by deprotecting reactive hydroxyl moieties. Various oxidative enzymes are known to catalyze this reaction at the expense of molecular oxygen, which may lead in the case of phenols/catechols to undesired side reactions (e.g., oxidation, polymerization). Here an oxygen-independent demethylation via methyl transfer is presented employing a cobalamin-dependent veratrol-O-demethylase (vdmB). The biocatalytic demethylation transforms a variety of aryl methyl ethers with two functional methoxy moieties either in 1,2-position or in 1,3-position. Biocatalytic reactions enabled, for instance, the regioselective monodemethylation of substituted 3,4-dimethoxy phenol as well as the monodemethylation of 1,3,5-trimethoxybenzene. The methyltransferase vdmB was also successfully applied for the regioselective demethylation of natural compounds such as papaverine and rac-yatein. The approach presented here represents an alternative to chemical and enzymatic demethylation concepts and allows performing regioselective demethylation in the absence of oxygen under mild conditions, representing a valuable extension of the synthetic repertoire to modify pharmaceuticals and diversify natural products. |
| Databáze: | OpenAIRE |
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