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Oxygenating Biocatalysts for Hydroxyl Functionalisation in Drug Discovery and Development
Author(s) -
Charlton Sacha N.,
Hayes Martin A.
Publication year - 2022
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202200115
Subject(s) - hydroxylation , monooxygenase , chemistry , biochemical engineering , drug discovery , biocatalysis , substrate (aquarium) , combinatorial chemistry , cytochrome p450 , organic chemistry , biochemistry , biology , catalysis , enzyme , engineering , reaction mechanism , ecology
C−H oxyfunctionalisation remains a distinct challenge for synthetic organic chemists. Oxygenases and peroxygenases (grouped here as “oxygenating biocatalysts”) catalyse the oxidation of a substrate with molecular oxygen or hydrogen peroxide as oxidant. The application of oxygenating biocatalysts in organic synthesis has dramatically increased over the last decade, producing complex compounds with potential uses in the pharmaceutical industry. This review will focus on hydroxyl functionalisation using oxygenating biocatalysts as a tool for drug discovery and development. Established oxygenating biocatalysts, such as cytochrome P450s and flavin‐dependent monooxygenases, have widely been adopted for this purpose, but can suffer from low activity, instability or limited substrate scope. Therefore, emerging oxygenating biocatalysts which offer an alternative will also be covered, as well as considering the ways in which these hydroxylation biotransformations can be applied in drug discovery and development, such as late‐stage functionalisation (LSF) and in biocatalytic cascades.