243671-40-1Relevant academic research and scientific papers
Unexpected subtilisin-catalyzed hydrolysis of a sulfinamide bond in preference to a carboxamide bond in N-acyl sulfinamides
Mugford, Paul F.,Magloire, Vladimir P.,Kazlauskas, Romas J.
, p. 6536 - 6537 (2005)
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. Copyright
Subtilisin-catalyzed resolution of N-acyl arylsulfinamides
Savile, Christopher K.,Magloire, Vladimir P.,Kazlauskas, Romas J.
, p. 2104 - 2113 (2007/10/03)
We report the first biocatalytic route to sulfinamides (R-S(O)-NH 2), whose sulfur stereocenter makes them important chiral auxiliaries for the asymmetric synthesis of amines. Subtilisin E did not catalyze hydrolysis of N-acetyl or N-butanoyl arylsulfinamides, but did catalyze a highly enantioselective (E > 150 favoring the (R)-enantiomer) hydrolysis of N-chloroacetyl and N-dihydrocinnamoyl arylsulfinamides. Gramscale resolutions using subtilisin E overexpressed in Bacillus subtilis yielded, after recrystallization, three synthetically useful auxiliaries: (R)-p- toluenesulfinamide (42% yield, 95% ee), (R)-p-chlorobenzenesulfinamide (30% yield, 97% ee), and (R)-2,4,6-trimethylbenzenesulfinamide (30% yield, 99% ee). Molecular modeling suggests that the N-chloroacetyl and N-dihydrocinnamoyl groups mimic a phenylalanine moiety and thus bind the sulfinamide to the active site. Molecular modeling further suggests that enantioselectivity stems from a favorable hydrophobic interaction between the aryl group of the fast-reacting (R)-arylsulfinamide and the S1′ leaving group pocket in subtilisin E.
Chiral N-Acyl-tert-butanesulfinamides: The "Safety-Catch" Principle Applied to Diastereoselective Enolate Alkylations
Backes, Bradley J.,Dragoli, Dean R.,Ellman, Jonathan A.
, p. 5472 - 5478 (2007/10/03)
Diastereoselective enolate alkylation reactions of N-acylsulfmamides and conversion of the alkylation products to a variety of enantiopure products are reported. Several sulfinamides were prepared in solution followed by acylation to provide N-acylsulfmamides. The N-acylsulfinamides were then evaluated in diastereoselective enolate alkylation reactions. Of the sulfinamides evaluated, tert-butanesulfinamide provided the highest diastereoselectivity. To establish the potential utility of sulfinamides as versatile auxiliaries, methods were developed for (1) the racemization-free acylation of tert-butanesulfinamide to prepare optically pure N-acyl-tert-butanesulfinamides, (2) the diastereoselective C-alkylation of N-acyl-tert-butanesulfmamides, (3) the conversion of the N-acyl-tert-butanesulfmamides to the active ester equivalent by N-alkylation and S-oxidation, and (4) the cleavage of the N-alkyl-N-acyl-tert-butanesulfonamides to give chiral alcohol, ester, amide, and carboxylic acid target compounds. These studies provide the groundwork for the development of sulfinamides as dual chiral auxiliaries and linkers for the multistep solid-phase synthesis of enantioenriched compounds.
