Ketones enzymatic

Mention should also be made here of the extensive use of poly(vinyl alcohol) in potentially biodegradable applications. At appropriate hydroxyl contents these polymers will dissolve in water (see Chapter 14) and can apparently be conveniently washed away after use as a water-soluble packaging. Biodegradation does, however, appear to be slow and first requires an oxidative step involving enzymatic attack to a ketone such as polyenolketone, which then biodegrades more rapidly. 

Much of the chemistry of monosaccharides is the familiar chemistry of alcohols and aldehydes/ketones. Thus, the hydroxyl groups of carbohydrates form esters and ethers. The carbonyl group of a monosaccharide can be reduced with NaBH4 to form an alditol, oxidized with aqueous Br2 to form an aldonic acid, oxidized with HNO3 to form an aldaric acid, oxidized enzymatically to form a uronic acid, or treated with an alcohol in the presence of acid to form a glycoside. Monosaccharides can also be chain-lengthened by the multistep Kiliani-Fischer synthesis and can be chain-shortened by the Wohl degradation. 

Table 3. (R)-Cyanohydrins by Enzymatic Formation from Ketones and Hydrocvamic Acid as well as (7 )-a-Hydroxy-a-methyl Carboxylic Acids by Hydrolysis...

Acyloins (a-hydroxy ketones) are formed enzymatically by a mechanism similar to the classical benzoin condensation. The enzymes that can catalyze reactions of this type arc thiamine dependent. In this sense, the cofactor thiamine pyrophosphate may be regarded as a natural- equivalent of the cyanide catalyst needed for the umpolung step in benzoin condensations. Thus, a suitable carbonyl compound (a -synthon) reacts with thiamine pyrophosphate to form an enzyme-substrate complex that subsequently cleaves to the corresponding a-carbanion (d1-synthon). The latter adds to a carbonyl group resulting in an a-hydroxy ketone after elimination of thiamine pyrophosphate. Stereoselectivity of the addition step (i.e., addition to the Stand Re-face of the carbonyl group, respectively) is achieved by adjustment of a preferred active center conformation. A detailed discussion of the mechanisms involved in thiamine-dependent enzymes, as well as a comparison of the structural similarities, is found in references 1 -4. 

Similarly to quantitative determination of high surfactant concentrations, many alternative methods have been proposed for the quantitative determination of low surfactant concentrations. Tsuji et al. [270] developed a potentio-metric method for the microdetermination of anionic surfactants that was applied to the analysis of 5-100 ppm of sodium dodecyl sulfate and 1-10 ppm of sodium dodecyl ether (2.9 EO) sulfate. This method is based on the inhibitory effect of anionic surfactants on the enzyme system cholinesterase-butyryl-thiocholine iodide. A constant current is applied across two platinum plate electrodes immersed in a solution containing butyrylthiocholine and surfactant. Since cholinesterase produces enzymatic hydrolysis of the substrate, the decrease in the initial velocity of the hydrolysis caused by the surfactant corresponds to its concentration. Amounts up to 60 pg of alcohol sulfate can be spectrometrically determined with acridine orange by extraction of the ion pair with a mixture 3 1 (v/v) of benzene/methyl isobutyl ketone [271]. 

After the first hydrolytic step, secondary alcohols seem to continue biodegradation through ketone, hydroxyketone, and diketone. Diketones then produce a fatty acid and a linear aldehyde which is further oxidized to fatty acid. Finally, these two fatty acids continue biodegradation by enzymatic 3 oxidation [410],... 

The synthesis of a-amino acids by reaction of aldehydes or ketones with ammonia and hydrogen cyanide followed by hydrolysis of the resulting a-aminonitrile is called the Strecker synthesis. Enzymatic hydrolysis has been applied to the kinetic resolution of intermediate a-aminonitriles [90,91]. The hydrolysis of (rac)-phenylglycine nitrile... 

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]. 

Enzymatic oxidations have been reported. Bacilus stearothermophilus, for example, oxidizes secondary alcohols to the ketone. 

While an active enzymatic mechanism produces acetoacetate from acetoacetyl-CoA in the liver, acetoacetate once formed cannot be reactivated directly except in the cytosol, where it is used in a much less active pathway as a precursor in cholesterol synthesis. This accounts for the net production of ketone bodies by the liver. 

An IL solvent system is applicable to not only lipase but also other enzymes, though examples are still limited for hpase-catalyzed reaction in a pure IL solvent. But several types of enzymatic reaction or microhe-mediated reaction have been reported in a mixed solvent of IL with water. Howarth reported Baker s yeast reduction of a ketone in a mixed solvent of [hmim] [PFg] with water (10 1) (Fig. 16). Enhanced enantioselectivity was obtained compared to the reaction in a buffer solution, while the chemical yield dropped. 

The strategy of manipulation of the macro-environment can be utilized for biotransformations. Thus, Zelinski and Kula (1997) have enzymatically reduced lipophillic ketones like 2-acetylnaphthalene using dimethylether of P-cyclodextrin in the organic phase. The use of cyclodextrin increases the solubility of the ketone by a factor of 147 resulting in high yields with excellent enantioseiectivity. 

Zinc hydroxide and alkoxide species are particularly relevant to catalytic processes, often forming the active species. The cooperative effects of more than one zinc ion and bridged hydroxides are exploited in some enzymatic systems. Zinc alkyl phosphate and carboxylate materials have been important in the formation of framework compounds, often containing large amounts of free space for the inclusion of guest molecules. Aldehyde and ketone compounds are of low stability due to the poor donor capabilities of the ligands however, a number of examples have recently been characterized. 

During the past few years, increasing numbers of reports have been published on the subject of domino reactions initiated by oxidation or reduction processes. This was in stark contrast to the period before our first comprehensive review of this topic was published in 1993 [1], when the use of this type of transformation was indeed rare. The benefits of employing oxidation or reduction processes in domino sequences are clear, as they offer easy access to reactive functionalities such as nucleophiles (e. g., alcohols and amines) or electrophiles (e. g., aldehydes or ketones), with their ability to participate in further reactions. For that reason, apart from combinations with photochemically induced, transition metal-catalyzed and enzymatically induced processes, all other possible constellations have been embedded in the concept of domino synthesis. 

Another very recent development in the field of enzymatic domino reactions is a biocatalytic hydrogen-transfer reduction of halo ketones into enantiopure epoxides, which has been developed by Faber, Bornscheuer and Kroutil. Interestingly, the reaction was carried out with whole lyophilized microbial cells at pH ca. 13. Investigations using isolated enzymes were not successful, as they lost their activity under these conditions [26]. 

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

In an effort to develop easy-to-use ketoreductase toolbox , we have surveyed the activity and enantioselectivity of a collection of ketoreductases (KRED) from various sources toward the reduction of a variety of ketones [90,91]. These studies served as a useful guideline for developing enzymatic processes for the production of optically pure chiral alcohols. For example, several chiral chlorohydrins of pharmaceutical importance were synthesized in both enantiomeric forms using the enzymes in this ketoreductase collection (Table 7.2) [92]. Further applications of this collection and other commercially available ketoreductases can be found in a recent review [9]. 

Van Deursen, R., Stampfer, W., Edegger, K. et al. (2004) Chemo- and stereo-selective biocatalytic reduction of a,/8-unsaturated ketones employing a chemo-tolerant ADH from Rhodococcus ruber DSM 44541. Journal of Molecular Catalysis B-Enzymatic, 31 (4-6), 159-163. 

Yang, Y., Zhu, D., Piegat, T.J. and Hua, L. (2007) Enzymatic ketone reduction mapping the substrate profile of a short-chain alcohol dehydrogenase (YMR226c) from Saccharomyces cerevisiae. Tetrahedron Asymmetry, 18 (15), 1799-1803. 

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. 

Krauueer, M., Hummel, W. and Groeger, H. (2007) Enantioselective one-pot two-step synthesis of hydrophobic allylic alcohols in aqueous medium through the combination of a Wittig reaction and an enzymatic ketone reduction. European Journal of Organic Chemistry, (31), 5175—5179. 

Vicenzi, J.T., Zmijewski, M.J., Reinhard, M.R. et al. (1997) Large-scale stereoselective enzymatic ketone reduction with in-situ product removal via polymeric adsorbent resins. Enzyme and Microbial Technology, 20, 494-499. 

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