Enzymatic Fluoromethylation as a Tool for ATP‐Independent Ligation.

S‐adenosylmethionine‐dependent methyltransferases are involved in countless biological processes, including signal transduction, epigenetics, natural product biosynthesis, and detoxification. Only a handful of carboxylate methyltransferases have evolved to participate in amide bond formation. In this report we show that enzyme‐catalyzed F‐methylation of carboxylate substrates produces F‐methyl esters that readily react with N‐ or S‐nucleophiles under physiological conditions. We demonstrate the applicability of this approach to the synthesis of small amides, hydroxamates, and thioesters, as well as to site‐specific protein modification and native chemical ligation. [ABSTRACT FROM AUTHOR]