Enzymatic Racemization of Amines Catalyzed by Enantiocomplementary ω‐Transaminases

Abstract

A strategy for the biocatalytic racemization of primary α-chiral amines was developed by employing a pair of stereocomplementary PLP-dependent ω-transaminases. The interconversion of amine enantiomers proceeded through reversible transamination by a prochiral ketone intermediate, either catalyzed by a pair of stereocomplementary ω-transaminases or by a single enzyme possessing low stereoselectivity. To tune the system, the type and concentration of a nonchiral amino acceptor proved to be crucial. Finally, racemization could be achieved by the cross-transamination of two different amines without a requirement for an external amino acceptor. Several synthetically and industrially important amines could be enzymatically racemized under mild reaction conditions.

Racemization of Secondary‐Amine‐Containing Natural Products Using Heterogeneous Metal Catalysts

“…In contrast to the racemization of sec ‐alcohols, the development of efficient approaches for DKR and racemization of amines has remained challenging . Mechanistically, the racemization of amines typically involves dehydrogenation followed by re‐addition of hydrogen to the initially formed imine.…”

Lipases: Valuable catalysts for dynamic kinetic resolutions

“…In addition to the use of racemases, biocatalytic racemizations have also been accomplished by means of reversible hydrogen transfer or ketone amination catalyzed by a low stereoselective (Musa et al, 2013;Voss et al, 2010) or two stereocomplementary dehydrogenases (Bodlenner et al, 2009;Gruber et al, 2007;Voss et al, 2010) and ω-transaminases (Koszelewski et al, 2011). It is worthy to note that these approaches lead to racemization of secondary alcohols (Gruber et al, 2007;Musa et al, 2013) and amines (Koszelewski et al, 2011), substrates whose racemization usually requires metal catalysis.…”

“…It is worthy to note that these approaches lead to racemization of secondary alcohols (Gruber et al, 2007;Musa et al, 2013) and amines (Koszelewski et al, 2011), substrates whose racemization usually requires metal catalysis. Application of these reactions in DKR process, however, is still to be done.…”

STD‐NMR‐Based Protein Engineering of the Unique Arylpropionate‐Racemase AMDase G74C

“…Racemases perform enzyme reactions under very mild conditions and have frequently been applied in multi‐enzyme systems 3. 4 Despite its high synthetic potential, however, racemisation is a difficult reaction, and the low reaction rate of racemases often creates bottlenecks. Recently, Baxter and co‐workers achieved a sixfold activity increase of N‐acyl amino acid racemase by directed evolution and increased the yield in the dynamic kinetic resolution of D ‐amino acids 3.…”