Catechol oxidation

One of the earliest reports of LO inhibition concerned the effects of ortho-dihydroxybenzene (catechol) derivatives on soybean 15-LO [58]. Lipophilic catechols, notably nordihydroguaiaretic acid (NDGA) (19), were more potent (10 /zM) than pyrocatechol itself. The inactivation was, under some conditions, irreversible, and was accompanied by oxidation of the phenolic compound. The orfAo-dihydroxyphenyl moiety was required for the best potency, and potency also correlated with overall lipophilicity of the inhibitor [61]. NDGA and other phenolic compounds have been shown by electron paramagnetic resonance spectroscopy to reduce the active-site iron from Fe(III) to Fe(II) [62] one-electron oxidation of the phenols occurs to yield detectable free radicals [63]. Electron-poor, less easily oxidized catechols form stable complexes with the active-site iron atom [64]. 

Humic acido from ooilo and ligniteo have been examined by ERR spectrometry. All samples showed a stable free organic radical content of about 1018 spins per gram. When these samples were converted to their sodium salts, a marked increase in radical content occurred. This was interpreted to indicate that a quinhydrone moiety exists in the humic acid macromolecule. Synthetic humic acid, prepared by oxidizing catechol in the presence of amino acids, also showed similar ERR spectra, as did selected quinhydrone model compounds. The radical moiety appeared to be stable to severe oxidation and hydrolytic conditions. Reduction in basic media caused an initial decrease in radical species continued reduction generated new radical species. A proposed model for humic acid based on a hydroxyquinone structure is proposed. 

The later is effective in oxidizing catechol to muconic add even under nitrogen (equation 28).1167 This reactive copper spedes172 has been variously formulated as a [Cu202]2- unit containing a superoxide or peroxide 02 unit,1169 which may then involve a postulated unit 1167... 

Pal et al. (1994) compared the catalysis of oxidative coupling reactions of various phenolic compounds by the enzymes, laccase and tyrosinase, and mineral catalyst, birnessite. Birnessite acts as a heterogeneous catalyst whereas laccase and tyrosinase function as homogeneous catalysts. Laccase and tyrosinase continue to oxidize catechol after repeated additions of the chemical, while birnessite lost its oxidizing activity after the first addition of catechol (Figure 2.20). In the case of birnessite,... 

By one-electron oxidation, catechols are transformed into semiquinone radicals. These are unstable species and, in solution, undergo dismutation to the corresponding quinone and a molecule of the initial catechol according to the reaction [43] (Fig. 6.3a). 

Tyrosinase is a copper-containing oxidase (Coche-Guerente et al, 2001 Forzani et al, 2000), which possesses the two different activities illustrated in Figure 57.12. In the first step, referred to as the hydroxylase or cresolase activity, molecular oxygen is used to hydroxylate phenol to form catechol. In the second step, known as the catecholase activity, the enzyme oxidizes catechol to o-quinone, which is simultaneously oxidized by oxygen to its original form, with the production of water. The o-quinone is electro-chemically active and can be reduced back to catechol, as illustrated above in Eq. (57.17). 

Tyrosinase Kinetics. Km values for the oxidation of a series of catechols are relatively small from 26 X 10" M for the most rapidly oxidized substrate to 4 X 10" M for the most poorly oxidized catechol, 4-NO2-catechol (Table IV). In the absence of precise knowledge of the mecha-... 

The rest of the malvidin-3-glucoside in Remy et al. could not be recovered by thiolysis, probably because it is in a flavene-type structure or there are additional linkages to the pigment such as vinyl condensation (9) (10). It has been reported that enzymatic oxidation of caffeic yields an o-quinone that will condense with malvidin-3-glucoside (11) and overall 520 nm absorbance decreases. Similarly, fIavan-3-ols could also react with anthocyanins through an oxidized catechol ring (non-enzymatic formation). Such products would have bonds between the tannin and anthocyanins that cannot be cleaved by mild acid. 

It is of interest that, based on conclusive experimental data, different types of complexes oxidize catechole by strikingly different reaction mechanisms (see Scheme 18) (213,289). Therefore, this is an excellent example to show that catalysts that are similar in terms of activity might differ considerably in terms of the reaction mechanism. More importantly strucmral and/or spectroscopic models of metaUoenzymes are not necessarily useful biomi-metic model complexes, even if they catalyze the reaction. 

Oxidation mechanisms for drug substances depend on the chemical structure of the drug and the presence of reactive oxygen species or other oxidants. Catechols such as methyl-dopa180 and epinephrine181 are readily oxidized to quinones, as shown in Scheme 45. 5-Aminosalicylic acid undergoes oxidation and forms quinoneimine,182 which is further degraded to polymeric compounds (Scheme 46).183 Ethanolamines such as procaterol are oxidized to formyl compounds (Scheme 47),184 whereas thiols such as 6-mercaptopurine,185... 

Oxidation. Durst and co-workers find that this combination rapidly oxidizes catechols to ortho-quinones and hydroquinones to para-quinones at -25 to 0°. Based on NMR and IR, yields are quantitative. In addition, anthrone is converted into bianthrone (75% isolated yield) and benzophenone hydrazone is oxidized to diphenyldiazomethane. 

Oxidation of catechol. Molecular oxygen activated by cuprous chloride in pyridine and in the presence of methanol oxidizes catechol (1) to the monomethyl ester of cw,c -muconic acid (2) in 70% yield. Of several catalysts, cuprous chloride is the most efficient. In the absence of methanol, only a trace of cw,cu-muconic acid is obtained. High concentrations of methanol result... 

Note that catechols (1,2-dihyroxybenzenes) are readily oxidized to o-quinones, l5 but the products are often sensitive to the electrophilic or nucleophilic species in the reaction medium. Catechol itself gives 125. Dimerization is as much a problem with catechols as with monophenols (see Table 3.4). The conversion of catechol to 125 used silver carbonate and it is noted that silver salts are the classical oxidation reagent for such transformations. Other reagent have been used to oxidize catechol derivatives, including ceric sulfate, lead tetraacetate, DDQ (2,3-dichloro-5,6-dicyano-l,4-benzoquinone), iodate, and periodate. ... 

The later is effective in oxidizing catechol to muconic acid even under nitrogen (equation... 

Enhanced Response to Catechols. An important problem in bio-electroanalytical chemistry is the determination of catechol compounds in the presence of ascorbic acid (vitamin C) ( ). The development of carbon fiber ultramicroelectrodes has allowed for the monitoring of these compounds iji vivo ( ). Because the oxidation potential of ascorbate is very similar to those of catechol compounds, because the concentration of ascorbate is at least an order of magnitude higher than that of the catechol species present in the brain (27), and because ascorbate may become involved in an electrocatalytic reaction sequence with oxidized catechol species leading to loss in voltammetric resolution (29,30), the ability to detect catechols in the presence of ascorbate is a non-trivial problem. 

Cuprous chloride pyridine Oxidative catechol ring opening Dicarboxylic acid monoesters... 

The triphenylarsine oxide-catechol complex has been shown to consist of a catechol molecule hydrogen-bonded to the oxygen of one arsine molecule through both OH groups." The O O contacts are 2.63 and 2.60 A. The two molecules suffer virtually no distortion in the formation of the complex. 

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