Horse liver alcohol dehydrogenase diol oxidation

Irwin, A.J. and Jones, J.B. (1977) Asymmetric syntheses via enantiotopicaUy selective horse liver alcohol dehydrogenase catalyzed oxidations of diols containning a prochiral center. Journal of the American Chemical Society, 99, 555-551. 

The latter were transformed into (+)-64, (-)-65 and (+)-66, respectively, in good yields. Lactone (+)-66 was also prepared in 37 % yield by stereospecific Horse Liver Alcohol Dehydrogenase (HLADH) catalyzed oxidation of the meso-diol 67. Lactones (-)-64 and (+)-64 are potentially interesting starting materials for the... 

Other microorganisms and isolated enzymes have been also used for the oxidation of alcohols (Figure 26).27 Horse liver alcohol dehydrogenase was used for the oxidation of meso diols (Figure 26 (d, e)).27e,f When one of the hydroxyl groups was oxidized, cyclization proceeded spontaneously, followed by the enzyme-catalyzed oxidation, giving chiral lactones. 

Horse liver alcohol dehydrogenase (HLADH) catalyzes the oxidoreduction of a variety of compounds [56,57], It has been demonstrated that HLADH catalyzes the stereospecihc oxidation of only one of the enantiotopic hydroxyl groups of acyclic and monocyclic meso-diols [58,59], The authors demonstrated the oxidation of meso exo- and endo-7-oxabicyclo [2.2. l]heptane-2,3-dimethanol to the corresponding enantiomerically pure y-lactones by HLADH. NAD+ and flavin adenine dinucleotide (FAD) at concentrations of 1 and 20 mmol, respectively,... 

The use of enzymes for the enantioselective oxidation of prochiral (or racemic) diols has proved to be of significant synthetic interest. A range of simple racemic 1,2-diols proved to be good substrates for a system involving coimmobilized horse liver alcohol dehydrogenase (HLADH) and aldehyde dehydrogenase (AldDH) with NAD cofactor recycling. This produced enantiomerically pure a-hydroxycarbox-ylic acids (Scheme 12). 

Figure 21. Electroenzymatic oxidation of w e o-diols to give enantiomerically pure lactones with horse liver alcohol dehydrogenase (HLADH) and PDMe" as redox catalysts at pH 7.8 and 150mV vs. Ag/AgCl reference [125].

The oxidation of aldehydes to carboxylic acids has been most extensively investigated with horse liver alcohol dehydrogenases (65-67, 69, 73). There are two distinct reactions the direct oxidation of aldehydes as their hydrated gem-diol form [reaction (9)] and the oxidation of hemiacetals to esters [oxidative esterification, reaction (10)]. 

Oxidation of 3-substituted pentane-l,5-diols catalysed by horse liver alcohol dehydrogenase furnishes chiral valerolactones. The transformation can be carried out on a synthetically useful scale (2g) in good chemical (75%) and optical (90%) yields, although bulky groups in the 3-position result in a falling-off of the latter (c/. ref. 83). 

Michael addition of the enolate (74) to ( )-ethyl crotonate leads to lactone (75) in an optical yield of 12%. A full report has appeared on an alternative preparation of (75) in quantities of up to 2 g by oxidation of 3-substituted pentane-1,5-diols using horse liver alcohol dehydrogenase. For the 3-methyl derivative (75), the optical yield is 78%, but this figure falls considerably with larger substituents. 

An enzymatic reaction of some synthetic importance is the enantioselective oxidation of meso diols by horse liver alcohol dehydrogenase HLADH.t i] Some representative examples follow ... 

Diols (65) can be oxidized regioselectively to butyrolactones (66) when = = Ph using benzoyl peroxide and nickel bromide or trityl tetrafluorobor-ate. ° When the substituents are simple alkyl groups, the oxidation is around 90% selective. A further use of horse liver alcohol dehydrogenase is in the oxidation of cyclic or acyclic me o-diols (e.g. 67), which results in the formation of optically pure lactones (e.g. 68). Yields are typically 65%, and the reactions can be run on up to 2 g quantities. 

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