ENANTIOSELECTIVE HYDROLYSIS OF SOME 3-(2-NITROPHENOXY) BUTANOATES CATALYZED BY PSEUDOMONAS-FLUORESCENS AND PSEUDOMONAS-SP LIPASE

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 >99%) 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 H-1-NMR shift reagents revealed 70-90 % e.e. for the remaining R-(-)-esters in hydrolyses of rac. 4, 6, and 9, and greater-than-or-equal-to 99 % e.e. in hydrolyses of rac. 7 and 10. A large effect on 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.