Biocatalysis asymmetric reduction

CCCs may obtain chiral compounds by classical resolution, kinetic resolution using chemical or enzymatic metlrods, biocatalysis (enzyme systems, whole cells, or cell isolates), fermentation (from growing whole microorganisms), and stereoselective chemistry (e.g., asymmetric reduction, low-temperature reactions, use of chiral auxiliaries). CCCs may also be CCEs by capitalizing on a key raw material position and going downstream. Along with companies manufacturing chiral molecules primarily for other purposes, such as amino acid producers, these will be the key sources for the asymmetric center. 

With the access to diverse and stable biocatalysts, more and more conventional chemical processes (first generation) in pharmaceutical manufacturing have been replaced by second-generation biocatalysis processes with substantial impact on the pharmaceutical industry. In this chapter, some commonly used biocatalytic reactions for chiral preparation, including hydrolytic reactions, acyl and glycosyl transfer reactions, asymmetric reduction/ oxidation reactions, and asymmetric formation of C-C bonds, are introduced and exemplified by the research achievements developed by the authors laboratory as well as other research groups. Some of the bioprocesses described herein have been successfully applied on pilot or even industrial scale. ... 

Application of biocatalysis towards asymmetric reduction and hydrolytic desymmetrisation in the synthesis of a P-3 receptor agonist. Green Chem., 13 (10), 2888-2894. 

In addition to further improvement of the efficiency of these systems, we believe that also a significant focus should be put on environmental and ethical issues associated with their large-scale application. Only if these aspects are taken into account during process development, biocatalysis can reach its full potential for sustainable asymmetric reduction reactions. 

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. 

Houng, J.-Y. and Liau, J.-S. (2003) Applying slow-release biocatalysis to the asymmetric reduction of ethyl 4-chloroacetoacetate. Biotechnol. Lett., 25,17-21. 

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... 

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

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. 

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]. 

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