Tetrahedron report number 203

Herein we review recent advances in the asymmetric reduction of ketones by biocatalysts. Included are discussions on recent developments in methodologies to control enantioselectivities of catalytic reactions, and examples of practical applications that reduce various types of ketones are also shown.

Recent developments in asymmetric reduction of ketones with biocatalysts

Redox reactions are important steps in the metabolism and energy conversion of living cells. Besides the enzymes necessary, a number of coenzymes are involved in such reactions: ferrodoxins, lipoic acid, NAD(H), NADP(H), flavins and cytochromes. The coenzymes differ in their redox potential, in the binding constants and the mode of regeneration [1]. NADH/NADPH are the most frequently encountered coenzymes. In general they dissociate easily and need a second reaction with another metabolite for regeneration. These properties are one of the means by which nature directs the flow of intermediates in response to biosynthetic needs. Because of the spectral properties of the coenzyme moiety, dehydrogenases have been extensively studied in the past [2] and have found widespread applications in clinical and food analysis [3].

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1989.tb14983.x

Dehydrogenases for the synthesis of chiral compounds

Microbial asymmetric reduction of ketones is a method widely used for the preparation of chiral alcohols. The present progress report deals with the basic concepts that govern enantioselectivity of enzymes and intact cells. Strategies to control the stereochemical course of microbial reductions of carbonyl compounds and the relationship of substrate structure to enantioselectivity are considered.

Microbial Asymmetric Catalysis—Enantioselective Reduction of Ketones [New Synthetic Methods (45)]

It has been known for many decades that chiral compounds can be obtained by stereospecific biocatalytic reduction. Further significant methodological developments in this field have, however, only been made during the past ten years; they include the application of previously unused microorganisms and electron donors, the discovery of additional substrates for the known reductases, the development of methods for regenerating reduced pyridine nucleotides, and the discovery of new reductases which were sought for specific preparative purposes. Many chiral compounds can now be synthesized by microbial hydrogenation using H2 and hydrogenase-containing microorganisms as well as by electromicrobial or electroenzymatic reduction. In the two latter methods, anaerobic or aerobic organisms are supplied with electrons from electrochemically reduced, artificial mediators, e.g., methyl viologen. Reductases that do not require pyridine nucleotides and can accept electrons directly from reduced viologens are especially useful. Two examples of this type of enzyme are described which are of preparative interest. Many cells contain methyl viologen-dependent NAD(P) reductases, a large number of which have still not been characterized. A productivity number is proposed which allows different methods of bioconversion with microorganisms to be compared. The productivity numbers of compounds synthesized by the methods described in this review are often 10- to 100-fold higher than those of substances obtained by conventional techniques.

Woan Ru Shieh

Papers

Stereochemical control of yeast reductions. 1. Asymmetric synthesis of L-carnitine