Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines

Transaminases (TAs) offer an environmentally and economically attractive method for the direct synthesis of pharmaceutically relevant disubstituted 1-phenylpropan-2-amine derivatives starting from prochiral ketones. In this work, we report the application of immobilised whole-cell biocatalysts with ( R )-transaminase activity for the synthesis of novel disubstituted 1-phenylpropan-2-amines. After optimisation of the asymmetric synthesis, the ( R )-enantiomers could be produced with 88-89% conversion and >99% ee, while the ( S )-enantiomers could be selectively obtained as the unreacted fraction of the corresponding racemic amines in kinetic resolution with >48% conversion and >95% ee. Immobilised whole-cell ( R )-transaminases (TAs) enabled synthesis of either ( R )- or ( S )-enantiomers of drug-like amines from prochiral ketones or from racemic amines, respectively, in >95% ee.