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Publication Abstract from PubMed

Catalytic selective hydroxylation of unactivated aliphatic (sp(3) ) C-H bonds without a directing group represents a formidable task for synthetic chemists. Through directed evolution of P450(BSbeta) hydroxylase, we realize oxyfunctionalization of unactivated C-H bonds in a broad spectrum of aliphatic carboxylic acids with varied chain lengths, functional groups and (hetero-)aromatic moieties in a highly chemo-, regio- and enantioselective fashion (>30 examples, Cbeta/Calpha>20 : 1, >99 % ee). The X-ray structure of the evolved variant, P450(BSbeta) -L78I/Q85H/G290I, in complex with palmitic acid well rationalizes the experimentally observed regio- and enantioselectivity, and also reveals a reduced catalytic pocket volume that accounts for the increased reactivity with smaller substrates. This work showcases the potential of employing a biocatalyst to enable a chemical transformation that is particularly challenging by chemical methods.

Biocatalytic Enantioselective beta-Hydroxylation of Unactivated C-H Bonds in Aliphatic Carboxylic Acids.,Zhang K, Yu A, Chu X, Li F, Liu J, Liu L, Bai WJ, He C, Wang X Angew Chem Int Ed Engl. 2022 Jul 11;61(28):e202204290. doi: , 10.1002/anie.202204290. Epub 2022 May 23. PMID:35536725^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.