Asymmetric Synthesis of Optically Pure Pharmacologically Relevant Amines Employing ω-Transaminases

Various omega-transaminases were tested for the synthesis of ertantiomerically pure amines from the corresponding ketones employing D- or L-alanine as amino donor and lactate dehydrogenase to remove the side-product pyruvate to shift the unfavourable reaction equilibrium to the product side. Both enantiomers, (R)- and (S)-amines, could be prepared with up to 99% ee and > 99% conversions within 24 h at 50 mM substrate concentration. The activity and stereoselectivity of the amination reaction depended on the omega-transaminase and substrate employed; furthermore the co-solvent significantly influenced both the stereoselectivity and activity of the transaminases. Best results were obtained by employing ATA-117 to obtain the (R)-enantiomer and ATA-113 or ATA403 to access the (S)-enantiomer with 15% v v(-1) DMSO.