Dehydrogenase-catalyzed oxidation

The two oxidoreductase systems most frequentiy used for preparation of chiral synthons include baker s yeast and horse hver alcohol dehydrogenase (HLAD). The use of baker s yeast has been recendy reviewed in great detail (6,163) and therefore will not be coveted here. The emphasis here is on dehydrogenase-catalyzed oxidation and reduction of alcohols, ketones, and keto acid, oxidations at unsaturated carbon, and Bayer-Vidiger oxidations. 

Alcohol dehydrogenases catalyze oxidation of alcohols in a reaction dependent on the pyridine nucleotide NAD+ [Eq. (5)]. Since the reaction is reversible, alcohol dehydrogenases also catalyze the reduction of aldehydes by... 

While most alkaloids do not contain aldehydes when they enter mammalian, microbial, or plant tissues, this functional group may become important when formed as a metabolite of alcohols (via alcohol dehydrogenase) or amines (via oxidative dealkylation and oxidative deamination). Aldehyde dehydrogenases catalyze oxidation of aldehydes to the corresponding carboxylic acids. The physical properties, catalytic mechanism, and specificity of this group of enzymes has been reviewed (99). The general reaction catalyzed by aldehyde dehydrogenase is seen in Eq. (9). 

Further transfer of the acyl group to coenzyme A is catalyzed by the same enzyme. This displacement reaction produces reduced lipoic acid. A third enzyme, dihydrolipoyl dehydrogenase, catalyzes oxidation of this product back to the disulfide form. The electrons lost in that oxidation are transferred first to an enzyme-bound flavin (not shown in the figure) and then to NAD +. ... 

KP Lok, TJ Jakovac, JB Jones. Enzymes in organic synthesis. 34. Preparation of enantiomerically pure exo- and endo-bridged bicyclic [2.2.1] chiral lactones via stereospecific horse liver alcohol dehydrogenase catalyzed oxidations of meso di-ols. J Am Chem Soc 107 2521-2526, 1985. 

Irwin, A.J. and Jones, J.B. (1977) Regiospedfic and enantioselective horse liver alcohol dehydrogenase catalyzed oxidations of some hydroxycydopentanes. Journal of the American Chemical Society, 99, 1525-1530. 

Figure 6. Fornation of optically pure secondary alcohols by yeast alcohol dehydrogenase catalyzed oxidation of racemic mixtures of alkan-2-ols and reduction of alkan-2-ones.

The MTT group has also been implicated in the intolerance to alcohol a.ssociatcd with certain injectable cephalosporins ccfamandole, cefotcian. ccfmetazolc, and cefoperazone. Thus, disulfiram-like reactions, attributed to the accumulation of acetaldehyde and resulting from the inhibition of aldehyde dehydrogenase-catalyzed oxidation of ethanol by M lT-contuining cephalo.sporins. " may occur in patients who have consumed alcohol before, during, or shortly after the course of therapy. 

Figure 16.2-3. Intrasequential regeneration of NAD(P) The strategy applied is the synthetic coupling of a dehydrogenase-catalyzed oxidation and a regeneration reaction yielding the final product and NAD(P) regeneration.

It should be mentioned at this point that most of the mediators described here were developed for analytical purposes. Only a few systems were applied to electrochemically driven dehydrogenase-catalyzed oxidations. This is partially because some systems exhibit moderate half-life times. 

NADH dehydrogenase Catalyzes oxidative phosphorylation reactions... 

Ribulose-5-phosphate is a pentose phosphate pathway intermediates produced by 6-phosphogluconate dehydrogenase catalyzed oxidation of 6-phosphogluconolactone. 

Describe how one could determine the rate of the alcohol dehydrogenase catalyzed oxidation of ethanol by NAD (Section 20.11). 

Figure 9. Alcohol dehydrogenase-catalyzed oxidation of ethanol with NAD. ...

Consider an example from the literature, a proton inventory for the equine liver alcohol dehydrogenase-catalyzed oxidation of ethanol with NAD (Chandra Sekhar Plapp, 1990) (Fig. 10). 

Figure 8. (A) Reaction progress curve for the yeast alcohol dehydrogenase-catalyzed oxidation of NADH with acetaldehyde and (B) the replot of the data from the progress curve according to the linear transformation of the rate equation (18.73) (Leskovac, 2000).

Nakata T, Kuwabara T, Tani T, Oishi T (1982) Total synthesis of (+)-oudemansin. Tetrahedron Lett 23 1015-1016 Nambiar KP, Stauffer DM, Kolodziej PA, Benner SA (1983) A mechanistic basis for the stereoselectivity of enzymatic transfer of hydrogen from nicotinamide cofactors. J Am Chem Soc 105 5886-5890 Ng GY, Yuan L-C, Jakovac IJ, Jones JB (1984) Enzymes in organic synthesis. 29. Preparations of enantiomerically pure cis-2,3- and 2,4-dimethyl lactones via horse liver alcohol dehydrogenase-catalyzed oxidations. Tetrahedron 40 1235-1243 Oae S, Nagata T, Yoshimura T, Fujimori K (1982) Reduction of diaryl disulfides with 1-benzyl-1,4-dihydronicotinamide. Tetrahedron Lett 3189-3192... 

This is the case with NAD(P)H-dependent dehydrogenases, where enzymes find applications in several synthetic processes (comprising the reduction of aldehydes, ketones, carboxylic acids, double, and triple carbon-carbon bonds), aimed at the preparation of chiral enantiopure bioactive compounds and of building blocks for fine chemicals and pharmaceutical products. Moreover, dehydrogenase-catalyzed oxidation reactions are gaining increasing interest as an environmentally friendly alternative to chemical oxidation processes, especially in those cases where a defined selectivity (either stereo-, regio-, or chemoselectivity) is required as well [1]. 

A. J. Irwin and J. B. Jones (1977), Regiospecific and enantioselective horse liver alcohol dehydrogenase catalyzed oxidations of some hydroxycyclopentanes. /. Amer. Chem. Soc. 99, 1625-1630. 

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