Transaminase-mediated synthesis of enantiopure drug-like 1-(3′,4′-disubstituted phenyl)propan-2-amines |
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| Authors: | Á gnes Lakó ,Zsó fia Molná r,Ricardo Mendonç a,Lá szló Poppe |
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| Affiliation: | Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rkp. 3, 1111 Budapest Hungary, +36-1-463-3299 ; Hovione Farmaciência, S.A., Campus do Lumiar, Edifício R, Estrada do Paço do Lumiar, 1649-038 Lisboa Portugal ; Biocatalysis and Biotransformation Research Center, Faculty of Chemistry and Chemical Engineering, Babes-Bolyai University of Cluj-Napoca, Arany János Str. 11, 400028 Cluj-Napoca Romania |
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| Abstract: | 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. |
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