The importance of ester and alkoxy type functionalities for the chemo- andenantio-recognition of substrates by hydrolysis with Candida rugosa lipase

Racemic esters of 1-phenyl- and 1-(pyridyl)ethyl acetates 1a-c (R = Me, Ph) were subjected to hydrolysis in water in the presence of Candida rugosa li pase (CRL). 1-Pyridylethyl acetates (1, R = Me) are hydrolyzed by crude CRL (C-CRL) and isopropanol (isopropyl alcohol) treated CRL (PT-CRL) at very l ow rates, and the enantiorecognition was disappointing. By using 1-pyridyle thyl benzoates (1, R = Ph) the results differed greatly: hydrolysis occurre d much faster, and the enantiorecognition was good for 3- and 4-pyridyl der ivatives and excellent for 2-pyridyl derivative. Analogous results were obt ained by submitting the 1-phenylethanol esters 4 to enzymatic hydrolysis un der the same experimental conditions. The hydrolysis of methyl o-acetoxyben zoates 7 (R = Me) gave quantitatively the deacetylated methyl o-hydroxybenz oates 9 (R = Me) by using either C-CRL or PT-CRL. A complete reversed selec tivity is observed in the hydrolysis of phenyl o-acetoxybenzoates 7 (R = Ph ) catalyzed by PT-CRL. Molecular modeling studies, aimed at probing the sub strate specificity and the enantioselectivity of enzyme in terms of its thr ee-dimensional structure is reported.