α-Keto Mesylate: A Reactive, Thiol-Specific Functional Group

Article abstract of DOI:10.1021/jo01303a030

A systematic study of the reactivity of α-keto mesylates with various nucleophiles (i.e., carboxylate, -OH, imidazole, -NH2, thiol acid anion, and -SH) under mildly basic conditions is reported. α-Keto mesylates do not react with imidazole or hydroxyl groups, react extremely slowly (if at all) with carboxylate and primary amines, and react several thousand times faster with thiols and thiol acid anions.The very rapid reaction with thiols occurs only with the dissociated thiolate anion.The addition of a β-hydroxyl group to α-keto mesylates accelerates the reaction with thiolate anions by a factor of 3-12 in acetone but has no effect on reactions run in dimethylformamide. α-Keto mesylates exhibit the same selectivity for thiolate anions, as compared to amines, as do α-keto chlorides.In view of this reactivity and selectivity, the α-keto mesylate appears to be a promising functional group for the electrophilic affinity labeling of biological macromolecules in weakly basic solutions.