Ketones biocatalytic asymmetric reduction

Nakamura K, Yamanaka R. Light mediated cofactor recycling system in biocatalytic asymmetric reduction of ketone. /. Chem. Soc. Chem. Commun. 2002 16 1782-1783. 

Kroutil and co-workers reported on a very efficient biocatalytic asymmetric reductive amination of ketones using co-transaminase as the enzyme for the synthesis of optically active a-chiral amines.Three enzyme systems were used for the successful operation of this methodology based on ... 

Enantiometrically pure alcohols are important and valuable intermediates in the synthesis of pharmaceuticals and other fine chemicals. A variety of synthetic methods have been developed to obtain optically pure alcohols. Among these methods, a straightforward approach is the reduction of prochiral ketones to chiral alcohols. In this context, varieties of chiral metal complexes have been developed as catalysts in asymmetric ketone reductions [ 1-3]. However, in many cases, difficulties remain in the process operation, and in obtaining sufficient enantiomeric purity and productivity [2,3]. In addition, residual metal in the products originating from the metal catalyst presents another challenge because of the ever more stringent regulatory restrictions on the level of metals allowed in pharmaceutical products [4]. An alternative to the chemical asymmetric reduction processes is biocatalytic transformation, which offers... 

An example of biocatalytic C=0 bond reduction has also been reported in the literature. The asymmetric reduction of ketones via whole-cell bioconversions and TH was tested by van Leeuwen et al. as complementary approaches to asymmetric... 

The chemoenzymatic synthesis of chiral alcohols is a field of major interest within biocatalytic asymmetric conversions. A convenient access to secondary highly enan-tiomerically enriched alcohols is the usage of alcohol dehydrogenases (ADHs) (ketoreductases) for the stereoselective reduction of prochiral ketones. Here, as in many other cases in asymmetric catalysis, enzymes are not always only an alternative to chemical possibilities, but are rather complementary. Albeit biocatalysts might sometimes seem to be more environmentally friendly, asymmetric ketone reduction... 

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. 

For the asymmetric biocatalytic reduction of ketones with in situ cofactor regeneration an enzyme-compatible biphasic reaction medium has been developed (Fig. 34) [53],... 

H. Groger, W. Hummel, R. Metzner, Reduction asymmetric biocatalytic reduction of ketones, in E. M. Carreira, H. Yamamoto (Eds.) Synthetic Methods/Comprehensive Chirality, Elsevier B.V., Amsterdam, 2012, pp. 181-215. 

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