Subtilisin-catalyzed resolution of N-acyl arylsulfinamides

Christopher K. Savile, Vladimir P. Magloire, Romas J. Kazlauskas

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2104-2113
Number of pages10
JournalJournal of the American Chemical Society
Volume127
Issue number7
DOIs
StatePublished - Feb 23 2005

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