Asymmetric catalysis biocatalysts

The main task in technical application of asymmetric catalysis is to maximize catalytic efficiency, which can be expressed as the ttn (total turnover number, moles of product produced per moles of catalyst consumed) or biocatalyst consumption (grams of product per gram biocatalyst consumed, referring either to wet cell weight (wcw) or alternatively to cell dry weight (cdw)) [2]. One method of reducing the amount of catalyst consumed is to decouple the residence times of reactants and catalysts by means of retention or recycling of the precious catalyst. This leads to an increased exploitation of the catalyst in the synthesis reaction. 

But there is still another point, not yet discussed but with considerable potential, which may also impact eventually on technical asymmetric catalysis. Even though biocatalysts are efficient, active, and selective, there still remains one big disadvantage At present, there is not yet an appropriate enzyme known or available for every given chemical reaction. It is estimated that about 25 000 enzymes exist in Nature, and 90% of these have still to be discovered [28, 29]. New biocatalysts are made available nowadays not only from screening known organism but also via screening metagenomic libraries and directed evolution techniques [30]. 

Turnover numbers (TONs) and substrate/catalyst ratios ([S]/[C] ratios) seem the preferred quantities in homogeneous catalysis, in contrast to biocatalyst loading (units L-1) and TTNs in biocatalysis. In the case of slow homogeneous chemical catalysts, the [S]/[C] ratio can approach unity (stoichiometric conditions). In the limit of no recycle, the values for TTN and TON are identical upon re-use of catalyst, TTN increases correspondingly. Whereas recycling is very important in biocatalysis, it does not seem to be common practice in homogeneous chemical asymmetric catalysis. 

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... 

The field of biocatalysis differs substantially from that of traditional chemical asymmetric catalysis. Whereas the range of optimal operational conditions may be broader for the latter case, the issue of substrate specificity of the former is more complex. The practical integration of biological catalysts into synthetic schemes has two main requirements (1) a suitable biocatalyst able to perform the required transformation must be identified and (2) the ability of the identified biocatalyst to perform the required transformation efficiently on the target substrate on a preparative scale must be assessed and if necessary engineered. Both of these requirements have been recognized and efforts to facilitate the implementation of biocataysts have been studied.2... 

Asymmetric catalysis encompasses the use of both biocatalysts (e.g., enzymes) and chemical catalysts that possess an element of chirality (e.g., a transition metal complex bearing a chiral ligand). From a commercial perspective, the interest in asymmetric catalysis emanates from inherent economic and ecological benefits that are associated with the capacity to produce a large volume of valuable enantiomerically enriched material through the agency of a negligible quantity of a chiral catalyst. Asymmetric catalytic processes may involve kinetic resolution of a racemic substrate, or preferably, direct transformation of a prochiral substrate into the desired chiral molecule. 

Table 2.14 gives an overview of industrial processes using asymmetric catalysis, including examples both of asymmetric hydrogenation and other types of reactions, as well as of the use of biocatalysts for the reaction. Selected chiral ligands used in asymmetric catalytic reactions are also shown in the table. 

There are many ways of organizing a monograph on industrial asymmetric catalysis. Rather than using the catalyst type (chemo- or biocatalyst) or the type of transformation (hydrogenation, oxidation, etc.), or the type or use of the target product... 

Enzymes are an attractive tool in asymmetric catalysis and efficiently complement traditional chemical methods [32,33]. The use of biocatalysts makes it possible to carry out chemical transformations without the need for laborious protection and deprotection steps [34]. Immobilized enzymes are preferred over free enzymes in solution, due to the possibility of repeated use, higher resistance to denaturing effects, and easy separation. The use of a structured support material could be an interesting alternative for conventional particulate enzyme carriers. When optimizing the use of immobilized enzymes, the immobilization method chosen is a very important factor to consider [35]. In this study, a reaction in an organic medium is considered most enzymes do not readily dissolve in organic media, and the enzyme will not detach from the support. This makes physical adsorption a very suitable technique to prepare a biocatalyst for use in an organic medium... 

Hummel, W., Abokitse, K., Drauz, K. et al. (2003) Towards a large-scale asymmetric reduction process with isolated enzymes Expression of an (5)-alcohol dehydrogenase in E. coli and studies on the synthetic potential of this biocatalyst. Advanced Synthesis and Catalysis, 345 (1 + 2), 153-159. 

The award of the Nobel Prize in Chemistry in 2001 to William R. Knowles and Ryoji Noyori for their work on metal-catalyzed enantioselective hydrogenation reactions and to K. Barry Sharpless for his work on catalyzed enantioselective oxidation reactions was a landmark in chiral catalysis studies. Enzymes and biocatalysts have also played a pivotal role as asymmetric catalysts [16]. 

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