Biocatalytic Desymmetrization of Prochiral 3-Aryl and 3-Arylmethyl Glutaramides: Different Remote Substituent Effect on Catalytic Efficiency and Enantioselectivity

Catalyzed by an amidase-containing Rhodococcus erythropolis AJ270 microbial whole cell catalyst in neutral phosphate buffer at 30 degrees C, desymmetric hydrolysis of a series of prochiral 3-aryl and 3-arylmethylglutaramides efficiently afforded 3-substituted glutaric acid monoamides in up to 95% yield and >99.5% ee. Even far away from the reaction site, the substituents on the aryl still have a significant effect on the catalytic activity and enantioselectivity and different remote substituent effect was observed for the two types of substrates. The synthetic application of biocatalytic desymmetrization was demonstrated by the facile transformation of the obtained enantiopure (R)-3-substituted 4-carbamoylbutanoic acid products to chiral dihydroquinolinone and delta-lactone compounds.