Examples for Biocatalytic Asymmetric Reductions

Geotrichum candidum NBRC 5767 (immobilized on water-adsorbent polymer) 

Horse liver alcohol dehydrogenase (HLADH) flnorinated NADH, ethanol 

Examples for biocatalytic reduction of carbonyl compoimds are described in Refs. [30-99]. 

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Finally, it is worth noting that significant advances have been made in the utilisation of biocatalytic methodologies for the (asymmetric) reduction of, for example, ketones to the corresponding alcohols (see later). 

For a long time, kinetic resolution of alcohols via enantioselective oxidation or via acyl transfer employing, for example, lipases along with dynamic kinetic resolution have been the biocatalytic methods of choice for the preparation of chiral alcohols. In recent years, however, impressive progress has been made in the use of alcohol dehydrogenases (ADHs) and ketor-eductases (KREDs) for the asymmetric synthesis of alcohols by stereoselective reduction of the corresponding ketones. Furthermore, recent remarkable multienzymatic systems have been successfully applied to the deracemisation of alcohols via stereoinversion based on an enantioselective oxidation followed by an asymmetric reduction. 

Dynamic kinetic resolution (DKR) of racemic substrate proceeds through asymmetric reduction when the substrate does racemize and the product does not under the applied experimental conditions. For example, by dynamic kinetic resolution of a-alkyl S-keto ester, one isomer, out of the four possible products for the unselective reduction (Scheme 33.18), can be selectively synthesized. Various examples of biocatalytic kinetic resolution through reduction are summarized in Scheme 33.19. A recent development in dynamic kinetic resolution has been reviewed. 

Asymmetric synthesis of sulfoxides can be achieved by biocatalytic oxidation of sulfides and reduction of sulfoxides (Figure 33). i4-27s One example is the reduction of alkyl aryl sulfoxides by intact cells of Rhodobacter sphaeroides f.sp. denitrificans (Figure 33 (a)). 341 In the reduction of methyl -substituted phenyl sulfoxides, ( S )-cnanliomcrs were exclusively deoxygenated while enantiomerically pure (W)-isomcrs were recovered in good yield. For poor substrates such as ethyl phenyl sulfoxide, the repetition of the incubation after removing the toxic product was effective in enhancing the ee of recovered (f )-enantiomers to 100%. 

The asymmetric syntheses of various chiral compounds have already been compared with regard to their applicability on a technical scale. For example, Blaser and coworkers compared four technically feasible routes (A-D) for the large scale preparation of the chiral building block ethyl (R)-2-hydroxy-4-phenylbutyrate (10) (Scheme 4.13) [53]. The stereogenic centre is introduced via enantioselective reduction, either via biocatalytic or nonenzymatic methods. 

In summary, a broad range of large-scale applicable biocatalytic methodologies have been developed for the production of L-amino acids in technical quantities. Among these industrially feasible routes, enzymatic resolutions play an important role. In particular, L-aminoacylases, L-amidases, L-hydantoinases in combination with L-carbamoylases, and /l-lactam hydrolases are efficient and technically suitable biocatalysts. In addition, attractive manufacturing processes for L-amino acids by means of asymmetric (bio-)catalytic routes has been realized. Successful examples are reductive amination, transamination, and addition of ammonia to rx,/fun-saturated carbonyl compounds, respectively. 

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