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

Ágnes Lakó; Zsófia Molnár; Ricardo Mendonça; László Poppe

doi:10.1039/d0ra08134e

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

RSC Adv. 2020 Nov 10;10(67):40894-40903. doi: 10.1039/d0ra08134e. eCollection 2020 Nov 9.

Authors

Ágnes Lakó^{1

2}, Zsófia Molnár¹, Ricardo Mendonça², László Poppe^{1

3}

Affiliations

¹ Department of Organic Chemistry and Technology, Budapest University of Technology and Economics Műegyetem rkp. 3 1111 Budapest Hungary poppe@mail.bme.hu +36-1-463-3299.
² Hovione Farmaciência, S.A., Campus do Lumiar Edifício R, Estrada do Paço do Lumiar 1649-038 Lisboa Portugal.
³ 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.

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.