Glyoxalase-based toolbox for the enantioselective synthesis of -hydroxy carboxylic acids

We report highly enantioselective synthesis of l-alpha-hydroxy carboxylic acids (l-alpha HCAs) via enzymatic intramolecular Cannizzaro reaction of (hetero)aryl glyoxals in the presence of glutathione-independent human glyoxalase DJ-1. Combined with the optimized synthesis of d-alpha HCAs using glyoxalases I and II, this approach offers a general, scalable and operationally simple access to both enantiomers of alpha-hydroxy acids in moderate to excellent yields with uniformly high enantioselectivity. Glyoxalases DJ-1 and GlxI/II were used for the enantioselective conversion of 13 (hetero)aryl glyoxals to l- and d-alpha-hydroxy carboxylic acids, respectively.