Biocatalytic Fluoroalkylation Using Fluorinated S-Adenosyl-l-methionine Cofactors

摘要

Modification of organic molecules with fluorine functionalitiesoffers a critical approach to develop new pharmaceuticals. Here, wereport a multienzyme strategy for biocatalytic fluoroalkylation using S-adenosyl-l-methionine (SAM)-dependent methyltransferases(MTs) and fluorinated SAM cofactors prepared from ATP and fluorinated l-methionine analogues by an engineered human methionine adenosyltransferasehMAT2A(I322A). This work introduces the first example ofbiocatalytic 3,3-difluoroallylation. Importantly, this strategy canbe applied to late-stage site-selective fluoroalkylation of complexmolecule vancomycin with conversions up to 99%.

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