Hydroxy acids, oxidation

The mechanism of flavin reduction in b2 has been a topic of debate for decades. Soon after it was discovered that DAAO could catalyze the elimination of Cl from chlorinated substrates, very similar experiments were conducted with many a-hydroxy acid oxidizing enzymes, including F 2- However, HCl elimination was not observed when using 3-Cl-lactate as a substrate. Studies using 3-Br-pynivate as an electron acceptor for lactate oxidation were interpreted as evidence of a carbanion mechanism of flavin reduction. ... 

LMO from Mycobacterium smegmatis is the best-studied example of this enzyme. The enzyme is an octomer of identical subunits, with one FMN per monomer. Even though no structural information has been obtained for LMO, much can be inferred from the high similarity of LMO to other ct-hydroxy acid oxidizing flavoenzymes. LMO exhibits many common properties of flavoprotein oxidases. It makes an N5 sulfite adduct and stabilizes anionic semiquinone and the benzoquinoid form of 8-mercapto-FMN," all of which are explained by the presence of a positive charge in the protein at the Nl—C2=0 locus. Sequence... 

L-lactate oxidase (LOX) catalyzes the oxidation of L-lactate to pyruvate with the concomitant reduction of the enzyme-hound FMN. The reduced enzyme is oxidized hy molecular oxygen resulting in oxidized enzyme and H207- LOX has substantial sequence homology to other a-hydroxy acid oxidizing flavoproteins, containing all the residues thought to he important for catalysis in this class of enzymes/... 

A contrasting mode of flavoprotein reactivity with an acetylenic inactivator occurs in the reaction of 2-hydroxy-3-butynoate (13, Fig. 15) with a number of a-hydroxy acid oxidizing enzymes. This process is exemplified by the inactivation of L-lactate oxidase from Mycobacterium smegmatis, an enzyme which catalyzes the oxidative decarboxylation of lactate to yield acetate, carbon dioxide, and water (Walsh, 1979, p. 408). Incubation of 13 with lactate oxidase leads to inactivation of the enzyme with a partition ratio that varies from 110 in the... 

L-Amino acid oxidase of rat kidney appears to catalyze the same type of reaction as n-amino acid oxidase. It oxidizes the monoamino, mono-carboxylic acids, but does not attack either dicarboxylic or polybasic compounds. Proline and W-methylamino adds are oxidized. A unique property of this enzyme is its ability to oxidize hydroxy acids. Only L-hydroxy acids are attacked. The ratio of hydroxy acid oxidation rate to amino acid rate is constant throughout purification. In general, hydroxy acid oxidation proceeds somewhat more rapidly than amino add oxidation, and the hydroxy acids corresponding to the basic amino adds... 

Reactions and Uses. The common reactions that a-hydroxy acids undergo such as self- or bimolecular esterification to oligomers or cycHc esters, hydrogenation, oxidation, etc, have been discussed in connection with lactic and hydroxyacetic acid. A reaction that is of value for the synthesis of higher aldehydes is decarbonylation under boiling sulfuric acid with loss of water. Since one carbon atom is lost in the process, the series of reactions may be used for stepwise degradation of a carbon chain. 

Interest in synthetic naphthenic acid has grown as the supply of natural product has fluctuated. Oxidation of naphthene-based hydrocarbons has been studied extensively (35—37), but no commercially viable processes are known. Extensive purification schemes must be employed to maximize naphthene content in the feedstock and remove hydroxy acids and nonacidic by-products from the oxidation product. Free-radical addition of carboxylic acids to olefins (38,39) and addition of unsaturated fatty acids to cycloparaffins (40) have also been studied but have not been commercialized. 

Although alcohol dehydrogenases (ADH) also catalyze the oxidation of aldehydes to the corresponding acids, the rate of this reaction is significantly lower. The systems that combine ADH and aldehyde dehydrogenases (EC 1.2.1.5) (AldDH) are much more efficient. For example, HLAD catalyzes the enantioselective oxidation of a number of racemic 1,2-diols to L-a-hydroxy aldehydes which are further converted to L-a-hydroxy acids by AldDH (166). 

Pyridazine N-ethoxycarbonylimide photolysis, 3, 13 Pyridazine, 4-gJycosyloxy-rearrangement, 3, 15 Pyridazine, halo-applications, 3, 56 Pyridazine, hexahydro-, 3, 40 photoelectron spectra, 2, 20-21 Pyridazine, hydrazino-reductive cleavage, 3, 34 synthesis, 3, 35 Pyridazine, hydroxy-acidity, 3, 4 Pyridazine, 3-hydroxyl-oxide... 

RUFF - FENTON Degradation Oxidative degradation of aldoses via a-hydroxy acids to lower chain aldoses. 

Glycol and o -hydroxy acid cleavage Oxidative decarboxylation Oxidative rearrangement of olefins... 

CHsjOH. CHlCgHg). CH(COOH). CH. COOH COOH. CHlCgHg). CH(CHaOH). CH. COOH COOH. CH(C2Hg). CH(COOH). CH. CH OH AomoPilopic acid is very stable, and is probably therefore the y-lactonic acid of one of these three hydroxy-acids. Further, pilopic acid seems to be produced from its higher homologue by loss of carbon dioxide and oxidation of the contiguous carbon atom. Of the four y-lactonic acids derivable from these three hydroxy-acids only two (I and II) answer these conditions,... 

In the early 1930 s, when the prime research aim was the commercial synthesis of the sex hormones (whose structures had just been elucidated), the principal raw material available was cholesterol extracted from the spinal cord or brain of cattle or from sheep wool grease. This sterol (as its 3-acetate 5,6-dibromide) was subjected to a rather drastic chromic acid oxidation, which produced a variety of acidic, ketonic and hydroxylated products derived mainly by attack on the alkyl side-chain. The principal ketonic material, 3j -hydroxyandrost-5-en-17-one, was obtained in yields of only about 7% another useful ketone, 3 -hydroxypregn-5-en-20-one (pregnenolone) was obtained in much lower yield. The chief acidic product was 3j -hydroxy-androst-5-ene-17j -carboxylic acid. All three of these materials were then further converted by various chemical transformations into steroid hormones and synthetic analogs ... 

Lead tetraacetate fragmentation has not been applied to the 20-hydroxy-18, 20-cyclo steroids. However, preferential cleavage of the 17,20-bond would be expected, as was observed in the chromic acid oxidation of a saturated 20-hydroxy-18,20-cyclo steroid in hot acetic acid which affords the 18-acetyl-17-ketone in 50-60% yield. 

Periodic acid oxidation (Section 25.23) Vicinal diol and a-hydroxy carbonyl functions in carbohydrates are cleaved by periodic acid. Used analytically as a tool for structure determination. 

The NAD- and NADP-dependent dehydrogenases catalyze at least six different types of reactions simple hydride transfer, deamination of an amino acid to form an a-keto acid, oxidation of /3-hydroxy acids followed by decarboxylation of the /3-keto acid intermediate, oxidation of aldehydes, reduction of isolated double bonds, and the oxidation of carbon-nitrogen bonds (as with dihydrofolate reductase). 

The much simpler steroid, 253, was fortuitously found to fulfill this role when injected into animals. Its lack of oral activity was overcome by incorporation of the 7a-thioacetate group. Reaction of the ethisterone intermediate, 77b, with a large excess of an organomagnesium halide leads to the corresponding acetylide salt carbonation with CO2 affords the carboxyllic acid, 251. This is then hydrogenated and the hydroxy acid cy-clized to the spirolactone. Oppenauer oxidation followed by treatment with chloranil affords the 4,6-dehydro-3-ketone (254). Conjugate addition of thiolacetic acid completes the synthesis of spironolactone (255), an orally active aldosterone antagonist. ... 

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