The base-promoted hydrolysis of amide substrates that contain a thiol substituent in the position α to the amide carbonyl group is effectively catalyzed by 4-heterocyclohexanones [Eq. (1)]. The proposed mechanism of the hydrolysis reaction mimics that employed by serine proteases, and involves equilibrium binding of the substrate to the catalyst, formation of an acyl-catalyst intermediate, and deacylation of the intermediate to release the product and regenerate the catalyst.