Deracemization transaminases

Scheme 11.13 Deracemization of racemic amino acids by cascade reactions, including DAAOs-catalyzed reactions and reductive amination reactions catalyzed either by amino acid dehydrogenases (a) or transaminases (b).

E.S. Park, J.S. Shin, Deracemization of amino acids by coupling transaminases of opposite stereoselectivity, Adv. Synth. Catal. 356 (17) (2014) 3505-3509. 

D. Koszelewsld, D. Pressnitz, D. Clay, W. Kroutil, Deracemization of mexiletine biocatalyzed by omega-transaminases, Org. Lett. 11 (21) (2009) 4810-4812. 

Transaminases can either be uhlized in kinetic resolution or as)unmetric synthesis (Scheme 29.3). Asymmetric synthesis, starting with a prochiral ketone substrate, can theoretically lead to 100% conversion and is usually the preferred route to chiral products (Scheme 29.3a). Furthermore high enantiomeric purity is not dependent on conversion rates, whereas a kinetic resolution (Scheme 29.3b) needs 50% conversion for a high enantiomeric excess (ee). But kinetic resolution is thermodynamically favored, if pyruvate is the amino acceptor, compared to as5munetric synthesis where the equilibrium lies on the substrate side [5,34]. To achieve 100% conversion, dynamic kinetic resolution serves as an alternahve with spontaneous deracemization or the initiation of a suitable racemate for enantiomerically pure substrates (Scheme 29.3c). Deracemization in a one-pot two-step reaction with an (S)-and (R)-selective transaminase, respectively, is a method of choice, but unfortunately two enantiocomplemen-tary enzymes are needed (Scheme 29.3d) [35]. Therefore deracemization with a dehydrogenase in the kinetic resolution step and a transaminase in the following step... 

General synthesis strategies for transaminase-catalyzed reactions. (a) Asymmetric synthesis with transaminase, (b) Kinetic resolution with transaminase, (c) Dynamic kinetic resolution with transaminase, (d) One-pot two-step deracemization with transaminase. 

The s)mthesis of all kinds of amino acids has been studied extensively in the last decades. Due to enhanced enzymatic and pharmacodynamic stability, as well as their diverse structures and biochemical properties, amino acids were maintained as chiral building blocks in numerous peptidomimetics, in single-enantiomer drugs, and also in various fields of agriculture [79,80]. Due to the wide substrate specificity of transaminases, these enzymes are suitable as biocatalysts for the amination of keto acids or deracemization of racemic amines to produce enantiopure amino acids [2,54,81]. 

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