Oxyfunctionalization of abundant carboxylic acids represents
a
direct approach to synthesizing α-hydroxy acids, which are valuable
intermediates of various active pharmaceutical ingredients. Although
ideal, the transformation is yet to be accomplished. Herein, enantiocomplementary
C(sp3)–H oxyfunctionalization for
the synthesis of α-hydroxy acids was realized by a cooperative
strategy of substrate engineering, homologue screening and protein
engineering of α-ketoglutarate-dependent nonheme iron aryloxyalkanoate
dioxygenases. The reaction provided concise synthetic routes toward
three types of 67 α-hydroxy acids with high efficiency and selectivity
(yield up to 90% and ee up to >99%). The distinctive
complementary reactions add to a growing repertoire of biocatalytic
oxyfunctionalization reactions.