PQQ-dependent Dehydrogenase Enables One-pot Bi-enzymatic Enantio-convergent Biocatalytic Amination of Racemic sec-Allylic Alcohols

Abstract

The asymmetric amination of secondary racemic allylic alcohols bears several challenges like the reactivity of the bi-functional substrate/product as well as of the α,β-unsaturated ketone intermediate in an oxidation-reductive amination sequence. Heading for a biocatalytic amination cascade with a minimal number of enzymes, an oxidation step was implemented relying on a single PQQ-dependent dehydrogenase with low enantioselectivity. This enzyme allowed the oxidation of both enantiomers at the expense of iron(III) as oxidant. The stereoselective amination of the α,β-unsaturated ketone intermediate was achieved with transaminases using 1-phenylethylamine as formal reducing agent as well as nitrogen source. Choosing an appropriate transaminase, either the (R)- or (S)-enantiomer was obtained in optically pure form (>98 % ee). The enantio-convergent amination of the racemic allylic alcohols to one single allylic amine enantiomer was achieved in one pot in a sequential cascade.

Keywords: Amination of alcohols; PQQ dependent dehydrogenase; allylic amines; biocatalytic cascade; sec-allylic alcohols; transaminases.

Scheme 1

Stereoselective amination of racemic allylic sec‐alcohols. Previous amination cascades employed alcohol dehydrogenase (ADHs), mostly two to transform both enantiomers or used TEMPO as oxidant.