Biocatalysis reduction

In order to broaden the field of biocatalysis in ionic liquids, other enzyme classes have also been screened. Of special interest are oxidoreductases for the enan-tioselective reduction of prochiral ketones [40]. Formate dehydrogenase from Candida boidinii was found to be stable and active in mixtures of [MMIM][MeS04] with buffer (Entry 12) [41]. So far, however, we have not been able to find an alcohol dehydrogenase that is active in the presence of ionic liquids in order to make use of another advantage of ionic liquids that they increase the solubility of hydrophobic compounds in aqueous systems. On addition of 40 % v/v of [MMIM][MeS04] to water, for example, the solubility of acetophenone is increased from 20 mmol to 200 mmol L ... 

Since stereoselectivities of biocatalytic reductions are not always satisfactory, modification of biocatalysis are necessary for practical use. This section explains how to find, prepare, and modify the suitable biocatalysts, how to recycle the coenzyme, and how to improve productivity and enantioselectivity of the reactions. 

The electrochemical rate constants for hydrogen peroxide reduction have been found to be dependent on the amount of Prussian blue deposited, confirming that H202 penetrates the films, and the inner layers of the polycrystal take part in the catalysis. For 4-6 nmol cm 2 of Prussian blue the electrochemical rate constant exceeds 0.01cm s-1 [12], which corresponds to the bi-molecular rate constant of kcat = 3 X 103 L mol 1s 1 [114], The rate constant of hydrogen peroxide reduction by ferrocyanide catalyzed by enzyme peroxidase was 2 X 104 L mol 1 s 1 [116]. Thus, the activity of the natural enzyme peroxidase is of a similar order of magnitude as the catalytic activity of our Prussian blue-based electrocatalyst. Due to the high catalytic activity and selectivity, which are comparable with biocatalysis, we were able to denote the specially deposited Prussian blue as an artificial peroxidase [114, 117]. 

With biocatalysis becoming increasingly accepted in synthetic organic chemistry on both the laboratory and industrial scale, there is a huge need for new complexes that can utilize electrons or hydrogen as redox equivalents in cofactor reduction. These redox equivalents are very inexpensive, readily available, and produce no side products, which in turn significantly facilitates the downstream processing of products. 

In each of these areas the relative merits of biocatalysis versus other catalytic methodologies will be assessed. Note that the text is given an asterisk ( ) when mention is made of a catalyst for a reduction or oxidation reaction that is featured in the later experimental section of this book. 

Biocatalysis is still an emerging field hence, some transformations are more established than others.Panke et alP have performed a survey of patent applications in the area of biocatalysis granted between the years 2000 and 2004. They found that although hydrolases, which perform hydrolyses and esterifications, still command widespread attention and remain the most utilized class of enzyme (Figure 1.5), significant focus has turned towards the use of biocatalysts with different activities and in particular alcohol dehydrogenases (ADHs) - also known as ketoreductases (KREDs) - used for asymmetric ketone reduction. 

Given the wide utility of biocatalysis in the fine chemical industry, why is there such an in-house reliance on classical methods of enantioseparation In fact, why is biocatalysis not applied more generally as a replacement for atom-inefficient or hazardous reactions that are intensively used in the pharmaceutical industry, such as amidation, reduction and oxidation ... 

Microbial reduction has been recognized for decades as a laboratory method of preparing alcohols from ketones with exquisite enantioselectivity. The baker s yeast system represents one of the better known examples of biocatalysis, taught on many undergraduate chemistry courses. Numerous other microorganisms also produce the ADH enzymes (KREDs) responsible for asymmetric ketone reduction, and so suitable biocatalysts have traditionally been identified by extensive microbial screening. Homann et have... 

Venkitasubramanian, P., Daniels, L. and Rosazza, J.P.N., Biocatalytic reduction of carboxylic acids mechanism and application. In Biocatalysis in the Pharmaceutical and Biotechnology Industries, Patel, R. (ed). CRC Press LLC Boca Raton, FL, 2006, pp. 425-440. 

Biological fuel cells have a long history in the literature,but in recent years, they have come to prominence as more conventional fuel cell technologies have approached mass-market acceptance. Driving the recent ascendance of biofuel cells are the aspects of biocatalysis that are unmatched by conventional low-temperature oxidation—reduction catalysts, namely, activity at near-room temperatures and neutral pH and, more importantly, selective catalytic activity. 

Oxidoreductases, which catalyze oxidation-reduction reactions and are acting, for example, on aldehyde or keto groups. An important application is the synthesis of chiral molecules, especially chiral PFCs (22 out of 38 chiral products produced on large industrial scale are already made using biocatalysis). 

The perspectives for an increasing use of biotechnology processes (biocatalysis, microbial fermentation) for LMW fine chemicals are promising. Substitution of traditional chemicals by biotechnology processes constitutes the most important means for reduction of manufacturing cost for existing fine chemicals. By 2010,30-60% of fine-chemical production processes are expected to comprise a biotechnology step ... 

The first sub-class of the oxido reductases is 1.1, and it comprises the dehydrogenases which act on primary or secondary alcohols or hemiacetals. They are mostly used for reduction of ketones and aldehydes. Two other categories are oxygenases and oxidases. The latter is not much used in biocatalysis. 

Bommarius, A. S., Drauz, K., Hummel, W., Kula, M.-R. and Wandrey, C. Some New Developments in Reductive Amination with Cofactor Regeneration. Biocatalysis 1994, 10, 37 7. 

The goal of this review is to highlight a progress in the transition-metal chemistry of some enzymes that catalyze oxidative and reductive reactions. These enzymes are referred to as oxidoreductases (1,2) and transition metals are usually found in their active sites. However, the discussion will not be devoted to these metals, which are absolutely essential for biocatalysis. Such information is brilliantly summarized in several recent fundamental reviews and monographs (3-9). 

It is clear from the examples in this book that the use of biocatalysis can produce some very cost-effective and environmentally acceptable processes, and the authors anticipate that the use of this technology will increase as synthetic organic chemists realize its value and begin to look for strategic disconnections in the synthetic sequence of new target molecules where a biocatalytic step can be applied to utmost benefit. Thus, biocatalysis should be seen as a routine part of the synthetic toolbox and, in some cases, the reagent of choice for transformations such as the reduction of ketones to chiral alcohols, and not as a technology of last resort when all else has failed. 

A. S. Bommarius, K. Drauz, W. Hummel, M.-R. Kula, and C. Wandrey, Some new developments in reductive animation with cofador regeneration, Biocatalysis 1994, 10, 37-47. 

Matsuda T, Yamanaka R et al (2009) Recent progress in biocatalysis for asymmetric oxidation and reduction. Tetrahedron Asymmetry 20 513-557... 

An emerging technique that takes advantage of the compatibility of aqueous chemistry and biocatalysis is the use of in situ reactions to promote deracemizations or DKRs.31 For example, reductive... 

Buchholz, S., and Groger, H. 2006. Enantioselective biocatalytic reduction of ketones for the synthesis of optically active alcohols. In Patel, R. N. (Ed.), Biocatalysis in the Pharmaceutical and Biotechnology Industries (pp. 757-790). Boca Raton FL CRC Press. 

Biocatalysis presents the advantages of high specificity, efficiency, energy conservation, and pollution reduction. Therefore, Biocatalysis and biotechnology are increasingly important for bioenergy production. 

The nitrile hydrates employed are selective and stop at the amide stage. However, they display no relevant enantioselectivity. The enantioselectivity in the processes is always introduced by an amidase (see for instance Schemes 6.27 and 6.28) in a second hydrolysis step. Overall the syntheses are, remarkably, often purely catalytic and combine chemical catalysis for reductions with biocatalysis for hydrolyses and the introduction of stereoinformation (Scheme 6.38). 

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