Chemo‐Enzymatic Deracemization Methods

Abstract

13 IntroductionIn recent times, the term deracemization has been used for describing techniques becoming increasingly important for the preparation of chiral compounds as single enantiomers. The term refers to a process in which one single enantiomer is obtained when starting from a racemate [1] .The two more common strategies for achieving such an objective are deracemization by stereoinversion or deracemization by dynamic kinetic resolution DKR (Scheme 13.1 ).Deracemization by stereoinversion is a process in which one form (S f ) of the racemic starting material (R f + S f ) is enantioselectively transformed into an intermediate (S i ) which can in turn react to give the form of opposite confi guration (R f ). An example of this method could be the selective oxidation of one enantiomer of a racemic secondary alcohol and the subsequent reduction with a catalyst of opposite stereopreference [2] .Deracemization by DKR is in principle a kinetic resolution process in which the non -transformed enantiomer is racemized in situ. The conditions are that a chiral catalyst promotes the transformation of one enantiomer (R s ) into the product (R p ) while the other enantiomer is racemized at a comparable rate and the racemic mixture (R s + S s ) is restored. The product (R p ) is not racemized under the same conditions. While a simple kinetic resolution yields a maximum of 50% of the product, with this technique a 100% conversion can be reached. Although the majority of chiral molecules of industrial interest are still prepared by kinetic resolution, the continuous development of industrial enzymes and racemizing processes fosters new chemo -or biocatalytic systems for DKR to appear. A great impulse for deracemization methods based on the one -pot/two -steps resolution racemization process was brought about by B ä ckvall et al . over a 10 -year period [3] .The method is of general applicability in the deracemization of secondary alcohols and amines and consists of a lipase -catalyzed irreversible acylation and in situ racemization of the non -reacted enantiomer catalyzed by a ruthenium catalyst,

Recombinant production of eight human cytosolic aminotransferases and assessment of their potential involvement in glyoxylate metabolism

“…Furthermore, aminotransferases are also important tools in biocatalysis, e.g. for the deracemization of natural and non-proteinogenic α-amino acids [36].…”

Overview on Multienzymatic Cascades for the Production of Non-canonical α-Amino Acids

“…strategy was proposed afterward by inclusion of a LAAO together a D-TA, using D-aspartate as the amino donor, which can be generated with an aspartate racemase (Tessaro et al, 2008). L-ABA was produced using an engineered DAAO/catalase module together with ω-TA (Seo et al, 2012).…”

“…A NADH-dependent lactate dehydrogenase was added in this system to transform the produced pyruvate, allowing to follow the course of the reaction spectrophotometrically; on the other hand, addition of this enzyme could also become a general idea to remove the pyruvate formed, avoiding putative transformation to L -Ala by α-TA (see above). An alternative strategy was proposed afterward by inclusion of a LAAO together a D -TA, using D -aspartate as the amino donor, which can be generated with an aspartate racemase ( Tessaro et al, 2008 ). L -ABA was produced using an engineered DAAO/catalase module together with ω-TA ( Seo et al, 2012 ).…”

Synthesis of enantiomerically pure alcohols and amines via biocatalytic deracemisation methods

“…To overcome the intrinsic disadvantage of KR reactions, a range of deracemisation protocols have been developed in the past years, which can be subdivided into different categories such as (1) dynamic kinetic resolution, (2) cyclic deracemisation, (3) stereoinversion and (4) enantioconvergent methods ( Scheme 2 ). 29 – 36 …”