Enzyme catalyzed reaction ketones

Biihler, H., Bayer, A. and Effenberger, F. (2000) Enzyme-catalyzed reactions, part 39. A convenient synthesis of optically active 5,5-disubstituted 4-amino- and 4-hydroxy-2(5f/)-furanones from (5)-ketone cyanohydrins. Chemistry - A European Journal, 6, 2564—2571. 

In a different NMR approach, deuterium-labeled p eM o-enantiomeric ketones are reduced to diastereomeric alcohols (theoretically by a hydrogenase), and the product ratio is measured by NMR spectroscopy 100). The method has yet to be tested in enzyme-catalyzed reactions. 

T. Ziegler, and S. Kuehner, Enzyme catalyzed reactions. 9. Enzyme-catalyzed synthesis of (R)-ketone cyanohydrins and their hydrolysis to (R)-a-hydroxy-a-methyl carboxylic adds, Tetrahedron Letters 1991,... 

Enzymes catalyzing reactions (19.8) and (19.9) are present in very minor amounts in the liver, and hence liver is a ketone body exporter rather than user. Acetoacetyl-CoA is converted to two acetyl-CoA molecules by the action of a thiolase, and the acetyl-CoA is used in the Krebs cycle. 1 mol /3-D-hydroxybutyrate... 

The nitroaldol (Henry) reaction, first described in 1859, is a carbon-carbon bondforming reaction between an aldehyde or ketone and a nitroalkane, leading to a nitroalcohol adduct [29]. The nitroalcohol compounds, synthetically versatile functionalized structural motifs, can be transformed to many important functional groups, such as 1,2-amino alcohols and a-hydroxy carboxylic acids, common in chemical and biological structures [18, 20, 30, 31]. Because of their important structural transformations, new synthetic routes using transition metal catalysis and enzyme-catalyzed reactions have been developed to prepare enantiomerically pure nitroaldol adducts [32-34]. 

Mitsunobu reaction [67], enzyme-catalyzed reactions [67], oxidation sec. alcohol —> ketone, reduction ketone —> alcohol [69]. 

Many of the observed attributes of enzymes arise by natural selection in order to help the host organism survive and reproduce. Benner et al. have proposed that one such attribute, the stereospecificities of dehydrogenases, has functional significance based on stereochemical arguments (18, 79). The central features of their functional model can be summarized as follows. The stereospecificities of dehydrogenases acting on alcohols are correlated with the equilibrium constant for the alcohol-carbonyl redox reaction as listed in Table IV (18). Enzymes catalyzing reactions where the eq is <10 " ilf transfer the pro-S proton from NADH when is >10"" Af, the pro-R proton is transferred. Thus the more readily reduced carbonyl compounds use the pro-R proton, but the more difficult to reduce carbonyl compounds use the pro-S proton. The proposed correlation is restricted to simple aldehydes and ketones (i.e., without additional chemistry that would influence the equilibrium constant, such as cyclizations of polyols or formation of lactones). The natural substrate of the enzyme must be well... 

There are, however, clear stereomechanistic differences between these two classes of enzyme-catalyzed reactions. The Claisen-type condensations uniformly involve inversion of configuration at the a-carbon of the esteratic substrate, involving C-C bond formation at either the re or the si face of the ketonic or aldehydic substrate (Table VII) (196-211). Moreover, neither Schiff bases nor metal ions have been directly implicated in the catalytic mechanisms of these enzymes. Unlike the aldolases, these enzymes do not catalyze rapid enolization of the nucleophilic substrate in the absence of the second substrate. Inversion of configuration suggests that at least two catalytic groups, perhaps operating in concert, facilitate C-C bond formation. Physicochemical measurements on citrate synthase are consistent with this interpretation of inversion of configuration. 

Oxidoreductases are of special interest for the enantioselective reduction of prochiral ketones [49]. Formate dehydrogenase from Candida boidinii was found to be stable and active in mixtures of [MMIM][MeS04] with buffer. The apphcation of alcohol dehydrogenases for enzyme-catalyzed reactions in the presence of water-miscible ionic liquids could make use of another advantage of these solvents they increase the solubility of hydrophobic compounds in aqueous systems. By addition... 

Reduction of the ketone group of the following keto ester occurs stereospedfically at the re face using NADH in an enzyme-catalyzed reaction. Draw the structure of the product and assign its configuration. 

At equilibrium, a mixture contains 3% dihydroxyacetone phosphate because the ketone carbonyl group is more stable than the aldehyde carbonyl group of glyceraldehyde 3-phosphate. Only glyceraldehyde-3-phosphate reacts in subsequent steps of glycolysis. However, as it is removed from the equilibrium mixture, more dihydroxyacetone phosphate is converted to glyceraldehyde-3-phosphate. Similar isomerization enediol intermediates occur in many enzyme-catalyzed reactions of carbohydrates. 

S-Cyanohydrins by Selective Cleavage of the R Form in a Racemate. In principle it should be possible to obtain S-cyanohydrins by selective enzymatic decomposition of the R enantiomer in a racemic mixture. This is difficult to achieve on a practical scale because the HCN that is liberated can engage in both enzyme-catalyzed and non-enzyme-catalyzed reactions by which the R enantiomer is again formed. This problem has been elegantly solved by Gotor and co-workers by combining this approach with that of the transcyanation [102]. A mixture of aldehyde and racemic cyanohydrin from a methyl ketone was treated with almond meal. The / -cyanohydrin of the methyl ketone was selectively cleaved and the / -cyanohydrin of the aldehyde was selectively formed by trans-... 

Today, the most promising synthesis of optically active cyanohydrins, especially with respect to the enantioselectivity of the reaction, is the enzyme-catalyzed addition of hydrogen cyanide to aldehydes and ketones, respectively. 

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. 

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 bioluminescence of the American firefly (Photinus pyralis) is certainly the best-known bioluminescent reaction, thanks to the work of Me Elroy and coworkers and E. H. White and his group (for references see P, p. 138, 6,168,169)) The substrate of this enzyme-catalyzed chemiluminescent oxidation is the benzothiazole derivative 107 (Photinus luciferin) which yields the ketone 109 in a decarboxylation reaction. The concept of a concerted cleavage of a dioxetane derivative has been applied to this reaction 170> (see Section II. C.). Recent experiments with 18C>2 have challenged this concept, as no 180-containing carbon dioxide was detected from the oxidation of 107 171>. 

In the case of the (1 )-configured olefinic ketones high conversion rates and enantiomeric excesses were achieved on the analytical and on the semi-preparative scale. With TBADH, which requires a slightly higher reaction temperature, decomposition of the halogenated substrates was observed. In the case of CPCR, which was used as a partially purified enzyme preparation from the parental strain, the formation of up to 50% of the fully saturated alcohols was observed (Scheme 2.2.7.18). Substrate (l )-33 could be converted into enantiopure (S)- and (R)- E)-32, respectively, by recLBADH- and HLADH/CPCR-catalyzed reaction. 

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