Unexpected Subtilisin-Catalyzed Hydrolysis of a Sulfinamide Bond in Preference to a Carboxamide Bond in N-Acyl Sulfinamides

Subtilisin Carlsberg-catalyzed hydrolysis of N-chloroacetyl p-toluenesulfinamide favored cleavage of the sulfinamide (S(O)−N) bond with a minor amount (∼25%) of the expected carboxamide (C(O)−N) bond. The sulfinamide hydrolysis was enantioselective (E ∼ 17) and yielded remaining starting material enriched in the R-enantiomer and achiral product, sulfinic acid and chloroacetamide, as confirmed by mass spectra and NMR. In contrast, the related subtilisin BPN‘ and E favored the carboxamide hydrolysis. Hydrolysis of the pseudo-symmetrical N-p-toluoyl p-toluenesulfinamide, which contains a sulfinamide and a carboxamide in similar steric and electronic environments, gave only sulfinamide cleavage (>10:1) for subtilisin Carlsberg, showing that sulfinamide cleavage is the preferred path even when a similar carboxamide is available.