Catechol intermediates

In 1996, the first successful combination of an enzymatic with a nonenzymatic transformation within a domino process was reported by Waldmann and coworkers [6]. These authors described a reaction in which functionalized bicy-clo[2.2.2]octenediones were produced by a tyrosinase (from Agaricus bisporus) -catalyzed oxidation of para-substituted phenols, followed by a Diels-Alder reaction with an alkene or enol ether as dienophile. Hence, treatment of phenols such as 8-1 and an electron-rich alkene 8-4 in chloroform with tyrosinase in the presence of oxygen led to the bicyclic cycloadducts 8-5 and 8-6 in moderate to good yield (Scheme 8.1). It can be assumed that, in the first step, the phenol 8-1 is hydroxylated by tyrosinase, generating the catechol intermediate 8-2, which is then again oxidized enzy-... 

In non-aqueous solution, the copper catalyzed autoxidation of catechol was interpreted in terms of a Cu(I)/Cu(II) redox cycle (34). It was assumed that the formation of a dinuclear copper(II)-catecholate intermediate is followed by an intramolecular two-electron step. The product Cu(I) is quickly reoxidized by dioxygen to Cu(II). A somewhat different model postulated the reversible formation of a substrate-catalyst-dioxy-gen ternary complex for the Mn(II) and Co(II) catalyzed autoxidations in protic media (35). 

Alternatively, upon sequential binding of catechol and 02 to the metal center, an Fem-superoxide-catechol intermediate is postulated to form [70], Oxygen insertion to form a lactone follows in steps similar to those shown in Figure 9. 

The hypothesis of Lintvedt and Thuruya about the formation of the dicopper-catecholate intermediate in the catalytic process [25] was soon after confirmed by... 

In 1985, the hypothesis about the formation of a dicopper-catecholate intermediate at the first stage of the catalytic reaction was further supported by Karlin and co-workers [30], who crystallized an adduct between tetrachlorocatechol (TCC) and a dicopper(II) complex with a phenol-based dinucleating ligand (Figure 5.5). This... 

Paroxetine appears to be slowly but well absorbed from the Gl tract following oral administration with an oral bioavailability of approximately 50%, suggesting first-pass metabolism (Table 21.8), reaching peak plasma concentrations in 2 to 8 hours. Food does not substantially affect the absorption of paroxetine. Paroxetine is distributed into breast milk. Approximately 80% of an oral dose of paroxetine is oxidized by CYP2D6 to a catechol intermediate, which is then either 0-methylated or 0-glucuronidated. These conjugates are then eliminated in the urine. 

CYP-catalyzed demethylenation of the methylenedioxyphenyl (1,3-benzdioxole) group in natural products and/or medicinal agents also results in quinone formation via the intermediate catechol intermediate. The mechanism (see Scheme 1) involves an initial hydroxylation at the methylene carbon followed by partitioning between demethylenation yielding a catechol intermediate and formaldehyde/formate or dehydration to a carbene (Murray, 2000). Further oxidation of the catechol generates the ort/zo-benzoquinone species. The selective serotonin reuptake inhibitor paroxetine is a classic example of a drug that undergoes this pathway (Zhao et al., 2007). As such, the mechanistic details of quinone formation with paroxetine will be discussed later (see Scheme 25). 

DOPA produced significant amounts of H2O2 and caused significant DNA damage, but the N-acetyl-DOPA did not. The extent of in vitro DNA damage is reduced considerably by treatment of the Cr( VI)/ catechol(amine) mixtures with catalase (EC 1.11.1.6), which shows that the DNA damage is H202-dependent and that the major reactive intermediates are likely to be Cr(V)-peroxo and mixed Cr(V)-catechol-peroxo complexes, rather than Cr(V)-catechol intermediates. 

The air oxidation of substituted catechols to the corresponding 0-benzoquinones is catalyzed by a variety of Cu(II)-amine systems. It appears that the mechanism involves the formation of a dicopper(II) catecholate intermediate electron transfer then occurs from the aromatic ring to give the o-benzoquinone and two Cu(I) centers. The latter then react with dioxygen and the catechol to regenerate the dicopper(II) catecho-late. A study of the effect of chloride ions on the kinetics of the copper-catalyzed oxidation of ascorbic acid by dioxygen does not rule out the involvement of Cu(I) intermediates but a mechanism involving Cu(III) is preferred. Kinetic studies on Cu(II)-catalyzed oxidation of enamines [e.g., equation (26)] and 3-phenylpropanal have been reported. 

Convergence of aerobic pathways for BTEX compounds leads to a catechol intermediate... 

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