No abstract

Abstract:Various w-transaminases were tested for the synthesis of enantiomerically 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 w-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 ATA-103 to access the (S)-enantiomer with 15% v v À1 DMSO.

All for one: A combination of three biocatalysts (ω‐transaminase, alanine dehydrogenase, and an enzyme such as formate dehydrogenase for cofactor recycling) catalyze a cascade to achieve the asymmetric transformation of a ketone into a primary α‐chiral unprotected amine through a formal stereoselective reductive amination (see scheme). Only ammonia and the reducing agent (formate) are consumed during this reaction.

(S)- as well as (R)-mexiletine [1-(2,6-dimethylphenoxy)-2-propanamine], a chiral orally effective antiarrhythmic agent, was prepared by deracemization starting from the commercially available racemic amine using omega-transaminases in up to >99% ee and conversion with 97% isolated yield by a one-pot two-step procedure. The absolute configuration could be easily switched to the other enantiomer, just by switching the order of the applied transaminases. The cosubstrate pyruvate needed in the first oxidative step was recycled by using an amino acid oxidase.