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 ( approximately 25%) of the expected carboxamide (C(O)-N) bond. The sulfinamide hydrolysis was enantioselective (E approximately 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.
Mugford
Paul F
PF
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montréal, Québec H3A 2K6, Canada.
Magloire
Vladimir P
VP
Kazlauskas
Romas J
RJ
D000577:Amides / Q000737:chemistry* / Q000378:metabolism*; D002384:Catalysis; D006868:Hydrolysis; D010196:Pancreatic Elastase / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity; D020860:Subtilisin / Q000737:chemistry* / Q000378:metabolism*; D013441:Sulfinic Acids / Q000737:chemistry* / Q000378:metabolism*; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism
D000577:Amides; D013441:Sulfinic Acids; D013449:Sulfonamides; C480101:beta-sultam; D010196:Pancreatic Elastase; D020860:Subtilisin