Enzyme-catalyzed resolution of N-acylsulfinamides via hydrolysis at the carbonyl or sulfinyl group

Sulfinimines are important chiral auxiliaries for asymmetric synthesis of amines. Enantiopure sulfinimines can be prepared from the direct condensation of enantiopure sulfinamides with aldehydes or ketones. However, few sulfinamides are available in enantiomerically pure form. To make a wider range of sulfinamides, we examined hydrolase-catalyzed resolution of N-acylsulfinamides. Using a fast screening method, we identified several hydrolases that catalyzed the hydrolysis of N-chloroacetyl-p-toluenesulfinamide with high to moderate selectivity. Scale-up reaction identified proteinase from Bacillus subtilis var. biotecus A that reacted at the carbonyl position and showed high enantioselectivity (E > 150) favoring the (R)-N-chloroacetyl-p-toluenesulfinamide. This hydrolase provided a new route to enantiopure p-chlorobenzenesulfinamide, benzenesulfinamide, p-methoxybenzenesulfinamide and 2,4,6-trimethylbenzenesulfinamide that cannot be prepared from current methods. We also identified proteinase, bacterial, which hydrolyzed N-acylsulfinamide at the sulfinyl yielding p-toluenesulfinic acid. The reaction occurred with enantioselectivity (E' ∼ 75) and provided enantiopure (S)-N-chloroacetyl-p-toluenesulfinamide.**Please refer to dissertation for diagram