Biocatalysis ketones

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 ... 

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. 

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... 

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. 

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. 

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. 

Sometimes called extractive biocatalysis. It was also successfully applied to ketone reduction (a) Vicenzi, J.T., Zmijewski, M.)., Reinhard, M.R., Landen, B.E., Muth, W.L. and Marier, P.G. (1997) Enzyme and Microbial Technology, 20, 494-499. 

Together with enantioselective hydrolysis/acylation reactions, enantioselective ketone reductions dominate biocatalytic reactions in the pharma industry [10], In addition, oxidases [11] have found synthetic applications, such as in enantioselective Baeyer-Villiger reactions [12] catalyzed by, for example, cyclohexanone monooxygenase (EC 1.14.13) or in the TEMPO-mediated oxidation of primary alcohols to aldehydes, catalyzed by laccases [13]. Hence, the class of oxidoreductases is receiving increased attention in the field of biocatalysis. Traditionally they have been perceived as difficult due to cofactor requirements etc, but recent examples with immobilization and cofactor regeneration seem to prove the opposite. 

For preparative purposes, the idea of correlation with some qualitative idea of solvent polarity is often sufficient, as implied here. There are numerous parameters which can be used to quantify the difference between solvents, but they all show some correlation with each other. By almost any measure, we would obtain the order hexane, toluene, methyl iso-butyl ketone, propanol. However, different parameters can give different rankings when more similar solvents are compared. For biocatalysis in non-aqueous media, there are few effects where the correct solvent scale can be confidently identified. However, it is useful to have an idea of two quite different classes of solvent scale. 

Within biocatalysis, redox reactions especially are often carried out in biphasic systems using crude cell systems, as the recycling of expensive cofactors is vital. The organic phase, which holds the rather insoluble substrate (and products), can be replaced by a more harmless IL. By this means, baker s yeast was used by Howarth and co-workers for enantioselective reduction of ketones [37]. In a 10 1 mixture of [BMIM][PF6] and water, reactions proceeded for a range of substrates giving yields and selectivities very comparable to those obtained by conventional methods [Eq. (8)]. 

Life uses enzymes to catalyse asymmetric reactions, so the question is—can chemists The answer is yes, and there are many enzymes that can be produced in quantities large enough to be used in the catalytic synthesis of enantiomerically pure molecules. This field—known as biocatalysis—melds ideas in chemistry and biology, and we do not have the space here to discuss it in detail. We leave you with just one example the reduction of a ketone to an alcohol with an enzyme known as a ketoreductase. 

The isolation and characterization of cyclohexanone monooxygenase (CHMO) from Acinetohacter sp. NCIB 9871 was reported in 1976 [68]. In addition to cyclohexanone and cydopentanone, CHMO was shown to be able to catalyze the oxidation of a variety of cyclic ketones to the corresponding lactones [69]. This attracted the attention of several other groups, which led to investigations of its mechanism [70, 71] as well as sequencing and doning [72]. It is by far the most extensively studied BVMO, and it has been used as a model system for up-scaling BVMO-mediated biocatalysis. 

Schiirmann, M., Lutje-Spelberg, (., Pitner, W.R., and Weuster-Botz, D. (2009) Wholecell biocatalysis evaluation of new hydrophobic ionic liquids for efficient asymmetric reduction of prochiral ketones. Enzyme Microb. Technol., 45, 310-316. 

Biphasic systems that include ionic liquids can also be applied to whole-cell biocatalysis. The ability of these solvents to act as a substrate reservoir and in situ extracting agent was demonstrated by an efficient asymmetric ketone reduction. 4-Chloroacetophenone was reduced to the key pharmaceutical intermediated (k)-l-(4-chlorophenyl) ethanol using Lactobacillus kefir cells in ILs. The indigenous cellular cofactor regeneration system remained active, which allowed high product concentrations without cofactor supplementation [34]. 

Enoate reductases (EC 1.3.1.31) are flavin-dependent and iron-sulfur-contain-ing proteins found among others in Clostridium species. Members of this NADHrflavin oxidoreductase/NADH oxidase family are distinguished from other ERs due to their high stereospecificity and strict regioselectivity for the reduction of double bonds of monoacids and monoesters, as well as reducing classical substrates such as a,p-unsaturated aldehydes, cyclic ketones, and methyl ketones. However, these enzymes are extremely oxygen sensitive, so they have not been employed in biocatalysis so far [2,3]. 

---