Optimized methods for the preparation of (S)-2-hydroxy-2-phenylpropanenitrile exploiting (R)-oxynitrilase in almond meal

Almond meal as the source of (R)-oxynitrilase was used for the resolution of rac-2-hydroxy-2-phenylpropanenitrile (1). Optimization was performed in the presence and absence of an aldehyde paying attention to the nature of the reaction medium (pH, buffer content and organic solvent). Under the optimized conditions, (S)-2-hydroxy-2-phenylpropanenitrile as the less reactive enantiomer was obtained at approximately 50% conversion and 98–99% ee, the (R)-counterpart decomposing enzymatically to acetophenone (3) and hydrogen cyanide. Hydrogen cyanide was conveniently bound by an aldehyde in the formation of the highly enantiopure (R)-aldehyde cyanohydrin. At pH>4.8, the presence of an aldehyde was necessary in order to prevent the reaction of (3) with hydrogen cyanide back to (R)-2-hydroxy-2-phenylpropanenitrile and the consequent racemization.