Ketone enzymatic reduction

Dynamic kinetic resolution of racemic ketones proceeds through asymmetric reduction when the substrate does racemize and the product does not under the applied experimental conditions. Dynamic kinetic resolution of a-alkyl P-keto ester has been performed through enzymatic reduction. One isomer, out of the four possible products for the unselective reduction (Figure 8.38), can be selectively synthesized using biocatalyst, and by changing the biocatalyst or conditions, all of the isomers can be selectively synthesized [29]. 

Figure 7.25 Enzymatic reduction of a-halogenated propargylic ketones by LBADH...

Zhu, D. and Hua, L. (2006) Enantioselective enzymatic reductions of sterically bulky aryl alkyl ketones catalyzed by a NADPH-dependent carbonyl reductase. The Journal of Organic Chemistry, 71 (25), 9484—9486. 

Asymmetric reduction of ketones or aldehydes to chiral alcohols has received considerable attention. Methods to accomplish this include catalytic asymmetric hydrogenation, hydrosilylation, enzymatic reduction, reductions with biomimetic model systems, and chirally modified metal hydride and alkyl metal reagents. This chapter will be concerned with chiral aluminum-containing reducing re-... 

In vitro studies on rat liver preparations confirmed the postulated metabolic pathway of nonenzymatic hydrolysis of the oxime 11.69 to the ketone 11.70, followed by enzymatic reduction to 11.71, hydroxylation to diols, and glucuronidation. Clearly, the first step in this metabolic scheme is the nearly quantitative hydrolysis of the oxime to the ketone. 

Surh YJ, Lee SS. (1992). Enzymatic reduction of shogaol a novel biotransformation pathway for the alpha, beta-unsaturated ketone system. Biochem Int. 27(1) 179-87. 

By analogy with the enantioselective reduction of prochiral ketones to chiral alcohols an attractive method for producing enantiomerically pure amines would be enantioselective reductive amination of a ketone via enzymatic reduction of an imine intermediate (Scheme 6.11). Unfortunately the required enzymes-amine... 

Enzymatic reduction of 23a with recLBADH and CPCR resulted in unsatisfactory results (60% and 49% ee) as well. The results mentioned above indicate that a bulky substituent at the alkyne moiety results in a higher selectivity of the reduction. Furthermore, Bradshaw et al. reported that Lactobacillus kefir ADH, an enzyme highly homologous to LB ADH, affords (R)-4-trimethylsilyl-3-butyn-2-ol [(R)-25j with an ee of 94% in 25% yield [39bj. In our investigations ketone 23b was reduced by recLBADH with almost quantitative conversion. The enantiomeric excess and absolute configuration of the product were determined by desi-lylation with borax converting alcohol (R)-25 into enantiopure (R)-3-butyn-2-ol [(R)-24j (Scheme 2.2.7.14). 

The enzymatic reduction of T-configured alkenones represents a valuable alternative to the enzyme-catalyzed reduction of the corresponding alkynone with subsequent partial reduction of the C-C triple bond. Nevertheless, since in our results the Z-configured vinylic alcohols are not accessible in enantiopure form by enzyme-catalyzed reduction of the olefinic ketones, for this class of compounds the two-step process via the propargylic alcohols is a highly valuable new strategy. 

Scheme 2.2.7.19 Chiral building blocks evolved from enantioselective enzymatic reduction of propargylic ketones D.

C. Wandrey, 1998, A novel reactor concept for the enzymatic reduction of poorly soluble ketones, J. Mol. Catal. B ... 

Substrate substituent effects on activity and enantioselectivity have been investi- gated in the enzymatic reduction of aryl ketones, using 24 recombinant ketoreduc-tases.308... 

A graduate student was studying enzymatic reductions of cyclohexanones when she encountered some interesting chemistry. When she used an enzyme and NADPH to reduce the following ketone, she was surprised to find that the product was optically active. She carefully repurified the product so that no enzyme, NADPH, or other contaminants were present. Still, the product was optically active. 

Fig. 34 Enzymatic reduction in biphasic media. Ketones are reduced enantioselective to the corresponding (S)-alcohols by ADH from Rhodococcus erythropolis. Regeneration of the cofactor NADH is carried out by FDH from C. boidinii. The introduction of a biphasic system allows higher substrate concentrations...

As before, the enzymatic reduction is the method of choice for the enantioselective reduction of purely aliphatic ketones and only in the case of fert-butyl methyl ketone could the bench mark of 90 % ee be crossed by the transfer hydrogenation and both other catalytic hydrogenation methods. However, substantial success in the hydrogenation of aromatic ketones by transition metal complexes with respect to the enantioselectivity and the activity (TON) strengthens the confidence that further progress is possible, enabling us to use some advantages of these nonenzymatic processes for extended application in the near future, for example in the facilitation of product isolation. 

Diols may be prepared by reduction of a-diketones or a-hydroxy ketones such as biacetyl, benzoin, and benzil. Substituted benzoins containing methoxyl and p-dimethylamino groups have been reduced catalytically over platinum oxide and by sodium amalgam and alcohol. Levorotatory propylene glycol is made from acetol, CHjCOCHjOH, by an enzymatic reduction with yeast. ... 

Pandit has provided evidence for the Lewis acid catalysis postulated to operate in these reduction reactions. The reduction of various cinnamoylpyridines by 1,4-dihydropyridine derivatives to the corresponding saturated ketones is catalyzed by zinc or magnesium cations. The reduction rate was fastest in the case of 2-cinnamoylpyridine, in which the metal ion can complex simultaneously to both the nitrogen and oxygen sites (Scheme 78). This example is regarded as a model of Lewis acid catalysis of the NADH-dependent enzymatic reduction of A -3-keto steroids. 

Baker s yeast reduces conjugated nitro compounds to nitroalkanes and also the C=C unit of conjugated ketones. Other enzymatic reductions are possible. A reductase from Nicotiana tabacum reduced a conjugated ketone to the saturated ketone, with excellent enantioselectivity. Enzyme YNAR-I and NADP-H reduces conjugated nitro compounds to nitroalkanes. ... 

Enzymatic Reduction A Chirai Aicohoi from a Ketone... 

Throughout the text most, but not all, of the 60 and 90 MHz nmr spectra have been replaced with 250 MHz proton spectra. A section on 2D nmr is included in the chapter on nmr spectroscopy, and procedures are given for the use of chiral nmr shift reagents to determine the optical purity of the product from the chiral enzymatic reduction of a ketone. 

Waxes mainly function as protective coatings, such as those found on leaf cuticles. They are mixtures of many constituents with high melting points, important members being esters of fatty acids with straight-chain saturated alcohols (fatty alcohols). The fatty acids and alcohols in these wax esters have similar chain lengths, mainly in the range C24 to C28. They have predominantly an even number of carbon atoms because the alcohols are biosynthesized from fatty acids by enzymatic reduction (Eqn 2.7). Lesser amounts of ketones, branched alkanes and aldehydes are present. 

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