Versatile Biocatalytic C(sp3 )-H Oxyfunctionalization for the Site- Selective and Stereodivergent Synthesis of α- and ß-Hydroxy Acids.

ABSTRACT

C(sp3 )-H oxyfunctionalization, the insertion of an O-atom into C(sp3 )-H bonds, streamlines the synthesis of complex molecules from easily accessible precursors and represents one of the most challenging tasks in organic chemistry with regard to site and stereoselectivity. Biocatalytic C(sp3 )-H oxyfunctionalization has the potential to overcome limitations inherent to small-molecule-mediated approaches by delivering catalyst-controlled selectivity. Through enzyme repurposing and activity profiling of natural variants, we have developed a subfamily of α-ketoglutarate-dependent iron dioxygenases that catalyze the site- and stereodivergent oxyfunctionalization of secondary and tertiary C(sp3 )-H bonds, providing concise synthetic routes towards four types of 92 α- and ß-hydroxy acids with high efficiency and selectivity. This method provides a biocatalytic approach for the production of valuable but synthetically challenging chiral hydroxy acid building blocks.