Biocatalytic hydrolysis of cyanohydrins:: an efficient approach to enantiopure α-hydroxy carboxylic acids

Rhodococcus erythropolis NCIMB 11540 was found to have a highly active nitrile hydratase/amidase enzyme system present which accepts the nitrile function of alpha-hydroxynitriles (cyanohydrins) as substrates. This biocatalytic hydrolysis using whole bacterial cells leads to alpha-hydroxy carboxylic acids which are much valued chiral building blocks in organic synthesis. Employing enantiopure cyanohydrins, which are easy available using (R)- or (S)-hydroxynitrile lyases, the products were obtained in high yield without racemization, decomposition or side reactions. Herein, the application of this biotransformation for preparative scale applications is described. To clarify the substrate acceptance of the nitrile hydrolyzing enzymes of R. erythropolis NCIMB 1] 540, several selected model compounds were subjected to biocatalytic hydrolysis. Reaction conditions were optimized to enable preparative scale conversions. In this manner, (R)-2-chloromandelic acid and (R)-2-hydroxy-4-phenylbutyric acid, two important pharmaceutical intermediates, were prepared in a gram scale. The substrate concentrations used were 9.3 and 13 g/l, respectively. The process yielded both acids in high optical (ee > 99 and 98%) and chemical (98%) yield after short reaction times (3 and 1.5 h). (C) 2003 Elsevier B.V. All rights reserved.