Highly Enantioselective Hydroxylation of 3-Arylpropanenitriles to Access Chiral β-Hydroxy Nitriles by Engineering of P450pyr Monooxygenase

Direct enzymatic hydroxylation of prochiral alkylnitriles represents a green and efficient synthesis of chiral beta-hydroxy nitriles, but reported examples are very inefficient and limited. Here we describe the development of an evolved P450pyr monooxygenase for enantioselective benzylic hydroxylation of alkylnitriles. By the use of an engineered P450pyr-D5M3 mutant, a variety of pharmaceutically relevant chiral aryl-substituted beta-hydroxy nitriles were prepared from prochiral 3-arylpropanenitriles in moderate yields with excellent enantioselectivities.

Automated summary

This article describes a green and efficient method for the synthesis of chiral β-hydroxy nitriles. By using an evolved P450pyr monooxygenase, various pharmaceutically relevant chiral aryl-substituted β-hydroxy nitriles were prepared from alkyl nitriles.