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A three-step one-pot biocatalytic cascade was designed for the enantioselective formal α-amination of hexanoic acid to L-norleucine. Regioselective hydroxylation by P450CLA peroxygenase to 2-hydroxyhexanoic acid was followed by oxidation to the ketoacid by two stereocomplementary dehydrogenases. Combination with final stereoselective reductive amination by amino acid dehydrogenase furnished L-norleucine in >97% ee.

Graphical abstract: Enantioselective biocatalytic formal α-amination of hexanoic acid to l-norleucine

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