Oxynitrilases: From Cyanogenesis to Asymmetric Synthesis

Abstract

Oxynitrilases are enzymes which catalyse the formation and cleavage of cyanohydrins. The cyanohydrin formation reaction proceeds by stereoselective addition of hydrogen cyanide to aldehydes or ketones to give enantiopure alpha-hydroxynitriles. This simple method of C-C bond formation has become a promising method to obtain a number of biologically active compounds. Cyanohydrin fission plays an important role in nature and is involved in plant defence where hydrogen cyanide is liberated upon plant damage. Among the known oxynitrilases only the (R)-oxynitrilase from Prunus amygdalus and the (S)-oxynitrilases from Hevea brasiliensis and Manihot esculenta are available in sufficient quantities which allow cyanohydrin formation on a larger scale. Prunus amygdalus oxynitrilase can easily be isolated from natural sources (bitter almond bran) and for two (S)-oxynitrilases functional overexpression allows their production in sufficient amounts for broad preparative applications. The three dimensional structure of the (S)-oxynitrilase from Hevea brasiliensis has been determined, and suggestions concerning the reaction mechanism have been discussed. Several procedures employing oxynitrilases have been developed to date which enable cyanohydrin formation on a preparative scale, particularly the use of buffer solutions as the reaction medium, organic solvents with immobilised enzymes, as well as biphasic reaction systems. Possible follow up reactions of the generated hydroxy and nitrile functionality, as well as the conversion of unsaturated cyanohydrins into valuable asymmetric compounds are outlined.