Microorganisms ketone reduction

In summary, ketoreductases have emerged as valuable catalysts for asymmetric ketone reductions and are preparing to enter the mainstream of synthetic chemistry of chiral alcohols. These biocatalysts are used in three forms wild-type whole-cell microorganism, recombinant... 

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... 

Biochemical reduction of a,/3-unsaturated ketones using microorganisms (best Beauveria sulfurescens) takes place only if there is at least one hydrogen in the /3-position and the substituents on a-carbons are not too bulky. The main product is the saturated ketone, while only a small amount of the saturated alcohol is formed, especially in slightly acidic medium (pH 5-5.5). The carbonyl is attacked from the equatorial side. Results of biochemical reduction of 5-methylcyclohex-2-en-l-one are illustrative of the biochemical reduction by incubation with Beauveria sulfurescens after 24 hours 74% of the enone was reduced to 3-methylcyclohexanone and 26% to 3-methylcy-clohexanol containing 55% of cis and 45% of trans isomer. After 48 hours the respective numbers were 70% and 30%, and 78% and 22%, respectively [878]. 

Figure 3. Ketone reduction by microorganisms. Ketones are selectively reduced to either S- or R-isomers...

Medici et al. have used a combined sequential oxidation-reduction to access a range of imsaturated secondary alcohols from their racemates [7] (Scheme 1). Here the S-alcohol 2 is oxidized by B. stereothermophilus which is displaying Prelog specificity leaving the l -enantiomer untouched. The other microorganism, Y. lipolytica contains an anti-Prelog dehydrogenase which is therefore able to reduce the ketone 1 to the l -alcohol 2. Thus the combination of the two steps effects a net deracemization of substrate 2. 

Reduction reactions mediated by microorganisms may include the reduction of nitro bonds, sulfoxide reduction, and reductive dehalogenation. Reduction of the nitro group to amine involves the intermediate formation of nitrase and hydroxy amino groups. Selected reductive reactions may involve the saturation of double bonds, reduction of aldehydes to alcohols or ketones to secondary alcohols, or of certain metals. The main reductive processes in the subsurface environment have been discussed earlier in this chapter. 

As already mentioned, the secondary alcohols that are obtained are optically active. It should be stressed that the reduction of ketones to carbinols by means of fermenting yeast is completely different from the method of resolution of racemic alcohols by treatment with living microorganisms (Pasteur). In the latter case one of the enantiomorphs is removed by oxidation during metabolism in the former it is produced by true asymmetric hydrogenation, without the intermediate formation of the inactive form, (Cf. Mayer and Levene and Walti. )... 

Diastereoselecdve hydroxylations are more common, for example Strepttmyces rimosus (NRRL 2234) will hydroxylate zearalenone (25) to give the (5)-8 -hydroxy derivative (26 equation 7). Other microorganisms gave reduction of the 6 -ketone group in (25). 

Capillary gas chromatographic determination of optical purities, investigation of the conversion of potential precursors, and characterization of enzymes catalyzing these reactions were applied to study the biogenesis of chiral volatiles in plants and microorganisms. Major pineapple constituents are present as mixtures of enantiomers. Reductions, chain elongation, and hydration were shown to be involved in the biosynthesis of hydroxy acid esters and lactones. Reduction of methyl ketones and subsequent enantioselective metabolization by Penicillium citrinum were studied as model reactions to rationalize ratios of enantiomers of secondary alcohols in natural systems. The formation of optically pure enantiomers of aliphatic secondary alcohols and hydroxy acid esters using oxidoreductases from baker s yeast was demonstrated. 

Microorganisms like baker s yeast are able to reduce some ferrocenyl ketones enantioselectively (for a review on microorganisms and enzymes for the reduction... 

Many microorganisms possessing alcohol dehydrogenases that are capable of reducing ketones and diketones have been demonstrated to produce chiral alcohols. Examples of such enantioselective reductions have been reviewed on many occasions (3-8). The main advantage of a secondary alcohol dehydrogenase for the production of chiral alcohols... 

Fuchs has used this reaction type for the construction of an 11-membered ring in the course of model studies for the [ll]cytochalasin synthesis. These cytostatic compounds, e.g. cytochalasin C (109), are metabolites of microorganisms. Reductive fragmentation of the benzenesulfonates (110 Scheme 37) produces the dienols (111). In contrast, both the sulfonates (112) on treatment with LDA afford the tricyclic ketones (113), the products of internal alkylation. Less than 1% of (111) is formed. In conclusion, the author points out that the enolate conformation (Scheme 37, in parentheses) appears to be all important in determining the reaction products of the four diastereoisomers (110) and (112). Whenever the enolate can easily assume a folded conformation, the tricyclic cyclobutane (113) will result. Models of the enolates of (110), where the intraannular fragmentation successfully occurs, show that the folded conformations are more strained than are the extended conformations. 

The differing abilities of trifluoromethyl and methyl groups to direct enantioselec-tion in the reduction of carbonyl substrates has also been analyzed using various other microorganisms including different strains of G. candidum, Hansenula anom-ala, Saccharomyces cervisiae, Streptomyces, etc.11751. The reduction of the cyclic ketone and enones shown in Fig. 15-29 was investigated. The differences in the electronic and steric properties of the trifluoromethyl and methyl residues resulted in different chemo- and enantioselectivities in the reduction of the phenylbutenones, while the cyclohexanones showed similar enantioselectivities. 

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