Enantioselective Hydrolysis of Some 3-(2-Nitrophenoxy)butanoates Catalyzed by Pseudomonas fluorescens and Pseudomonas sp. Lipase

Article abstract of DOI:10.1016/S0957-4166(00)86075-9

Racemic methyl, ethyl and cyanomethyl 3-(2'-nitrophenoxy) butanoates 4-10, chiral precursors of 2,3-dihydro-1,5-benzoxazepin-4(5H)-ones with ACE inhibitory activity, were prepared and submitted to kinetic resolution by a series of commercially available lipases.Best results (e.e.'s > 99percent) were obtained with Pseudomonas fluorescens and Pseudomonas sp. lipase.The structure of the alkyl ester group influences the rate of hydrolysis.Cyanomethyl esters 5 and 8 were more reactive than alkyl esters 4,6,7,9 and 10.Chiral 1H NMR shift reagents revealed 70-90percent e.e. for the remaining R-(-)-esters in hydrolyses of rac. 4, 6, and 9, and <*> 99percent e.e. in hydrolyses of rac. 7 and 10.A large effect of the rate and enantioselectivity of the hydrolysis of esters 4, 6, and 9, is observed when a methyl group, which is remote from the chiral center and from the reactive ester group, is on the aromatic ring.