Enzyme-Catalyzed Preparation and Synthetic Applications of Optically Active Cyanohydrins

Abstract

Chiral cyanohydrins are widespread in nature as cyanoglycosides, serving more than two thousand plants and many insects as antifeedant. Fast release of HCN from cyanohydrins in cells is catalyzed by hydroxynitrile lyases (HNLs). The importance of HNLs in organic syntheses is the enantioselectivity of cleavage as well as formation of cyanohydrins by these biocatalysts. For the preparation of (R)-cyanohydrins from aldehydes and HCN on a preparative scale, (R)-PaHNL from bitter almonds proves to be the best catalyst. For the synthesis of (S)-cyanohydrins, the recombinant HNLs from cassava (MeHNL) and rubber tree (HbHNL) are most suitable. In organic solvents or in biphasic systems, the chemical addition of HCN to the carbonyl compounds can be suppressed, resulting in high optical yields of the obtained cyanohydrins. Stereoselective follow-up reactions of (R)- and (S)-cyanohydrins lead to other important classes of compounds with stereogenic centers. Starting from (R)-cyanohydrins, (R)-2-hydroxy carboxylic acids, (R)-2-hydroxy aldehydes, (R)-2-hydroxy ketones, (1R)-2-amino alcohols, and (1R,2S)-2-amino alcohols are easily obtainable in high optical and chemical yields by transformation of the cyano group. Analogous transformations are possible starting from (S)-cyanohydrins. Sulfonylation of the OH function in cyanohydrins allows nucleophilic substitution of the sulfonate group with complete inversion of configuration. In this way, starting, e.g., from (R)-cyanohydrins, (S)-2-azido nitriles, (S)-2-amino nitriles, (S)-2-amino acids, (S)-1,2-diamines and (S)-2-sulfanyl nitriles are obtained in high optical yields.