Catechol derivatives

The hexacoordinate silicon dianions in pyridinium tris(o-phenylenedioxy)siliconate have been examined by X-ray diffraction by Flynn and Boer (157). 

The oxygen atoms are only slightly distorted from octahedral symmetry. The correct formulation is [C6H,NH]2 [(CgH40s)3Si] . 

The reaction of silica with catechol, pyrocatechol, and 2,3-naphthalenediol has been studied by several investigators (158-162), but Bartels and Erlenmeyer appear to have been the only ones to use this reaction to characterize the rate of depolymerization of silica (163a). For example, monomeric silicic acid from ethyl silicate in a standard solution of catechol in 0.8 N HCl reacted rapidly and could be titrated to a constant pH of 8.5 with an equivalent amount of standard NaOH solution in a few minutes. An equivalent amount of silica gel required 2.5 hr, but ignited gel reacted only slightly in 5 hr. The rate of reaction, followed by a constant pH titration, provides a way to estimate the relative degree of polymerization of silica or possibly the specific surface area. 

Baumann (163b) examined the relative stabilities of the six-coordinated silicon complex anions of some catechol derivatives. He measured the equilibrium constant K and also the pH at which 99% of the silicon in a solution containing 60 ppm silica as monomer is complexed when the concentration of the agent is 0.1 M. 

Baumann also examined the details of the reaction of silicic acid with catechol (163c) as well as with a catechol-formaldehyde condensate which acted as a polyphenol (163d). The latter resin, when not too highly cross-linked, removes soluble silica from slightly alkaline water. 

---

Catechol Derivatives. An elegant synthesis of trimethoxybenzaldehyde [86-81-7] (4) starting from quaiacol [90-05-1] (5) and formaldehyde (75) has been developed. The reaction sequence is as follows ... 

Various chemical species influence the rates of hydrolysis of penicillins, e.g. metal ions (Cu >Zn >Ni Co ) (80JCS(P2)1725), carbohydrates (78MI51101), certain amine-containing catechol derivatives (69JPS1102) and /3-cyclodextrin (71JA767). Some of these even show some of the characteristics of enzyme-catalyzed hydrolyses. 

The main product of the Elbs reaction is the 1,4-dihydroxybenzene (hydro-quinone). If the para position is already occupied by a substituent, the reaction occurs at an ortho position, leading to a catechol derivative although the yields are not as good as for a hydroquinone. Better yields of catechols 7 can be obtained by a copper-catalyzed oxidation of phenols with molecular oxygen ... 

Catechol is also obtained from coal coking and from certain wood residues. Vanillin (synthetic vanilla flavoring) is a catechol derivative. Resorcinol and hydroquinone are currently made by the same type of chemistry used... 

There is also some evidence for subtypes of COMT but this has not yet been exploited pharmacologically. Certainly, the majority of COMT is found as soluble enzyme in the cell cytosol but a small proportion of neuronal enzyme appears to be membrane bound. The functional distinction between these different sources of COMT is unknown. COMT inhibitors also exist (e.g. pyrogallol), mostly as catechol derivatives, but so far, most have proved to be highly toxic. Only recently have drugs been developed which are selective for COMT one of these agents, tolcapone, is used currently in treatment of Parkinson s disease (see Chapter 15). 

HT is metabolised primarily by MAO to 5-hydroxyindoleacetic acid (5-HIAA) (Fig. 9.4). In vitro, 5-HT is the preferred substrate for the MAOa, rather than the MAOb isoenzyme (see Chapter 8) and this appears to be the case in vivo since MAOa, but not MAOb, knock-out mice have increased concentrations of 5-HT in the brain. Obviously, because of its indole nucleus, 5-HT is not a substrate for the enzyme COMT which metabolises the catechol derivatives, dopamine and noradrenaline. However, other metabolic products of 5-HT are theoretically possible and one, 5-hydroxytryptophol,... 

Conjugate addition of vinyl-, aryl-, heteroarylcuprates 90 to the cyclobutenedione 63, followed by in situ protection with (methoxyethoxy) methyl chloride of the enolates, provides a method for synthesizing substituted catechol derivatives 91 [44], Regiocontrolled synthesis is achieved by using cyclobutenedione monoacetals 92 as starting substrates. (Scheme 32)... 

Various hydroxyl and amino derivatives of aromatic compounds are oxidized by peroxidases in the presence of hydrogen peroxide, yielding neutral or cation free radicals. Thus the phenacetin metabolites p-phenetidine (4-ethoxyaniline) and acetaminophen (TV-acetyl-p-aminophenol) were oxidized by LPO or HRP into the 4-ethoxyaniline cation radical and neutral V-acetyl-4-aminophenoxyl radical, respectively [198,199]. In both cases free radicals were detected by using fast-flow ESR spectroscopy. Catechols, Dopa methyl ester (dihydrox-yphenylalanine methyl ester), and 6-hydroxy-Dopa (trihydroxyphenylalanine) were oxidized by LPO mainly to o-semiquinone free radicals [200]. Another catechol derivative adrenaline (epinephrine) was oxidized into adrenochrome in the reaction catalyzed by HRP [201], This reaction can proceed in the absence of hydrogen peroxide and accompanied by oxygen consumption. It was proposed that the oxidation of adrenaline was mediated by superoxide. HRP and LPO catalyzed the oxidation of Trolox C (an analog of a-tocopherol) into phenoxyl radical [202]. The formation of phenoxyl radicals was monitored by ESR spectroscopy, and the rate constants for the reaction of Compounds II with Trolox C were determined (Table 22.1). 

Fe(III) displacement of Al(III), Ga(III), or In(III) from their respective complexes with these tripodal ligands, have been determined. The M(III)-by-Fe(III) displacement processes are controlled by the ease of dissociation of Al(III), Ga(III), or In(III) Fe(III) may in turn be displaced from these complexes by edta (removal from the two non-equivalent sites gives rise to an appropriate kinetic pattern) (343). Kinetics and mechanism of a catalytic chloride ion effect on the dissociation of model siderophore-hydroxamate iron(III) complexes chloride and, to lesser extents, bromide and nitrate, catalyze ligand dissociation through transient coordination of the added anion to the iron (344). A catechol derivative of desferrioxamine has been found to remove iron from transferrin about 100 times faster than desferrioxamine itself it forms a significantly more stable product with Fe3+ (345). 

Palladium-catalyzed reactions of arylboronic acids have been utilized to craft precursors for constructing indole rings. Suzuki found that tris(2-ethoxyethenyl)borane (149) and catechol-derived boranes 150 readily couple with o-iodoanilines to yield 151, which easily cyclize to indoles 152 with acid [158]. Kumar and co-workers used this method to prepare 5-(4-pyridinyl)-7-azaindoles from 6-amino-5-iodo-2-methyl-3,4 -bipyridyl [159], A similar scheme with catechol-vinyl sulfide boranes also leads to indoles [160]. A Suzuki protocol has been employed by Sun and co-workers to synthesize a series of 6-aryloxindoles [161]. 

It was found that catechol derivatives in general were able to protect cholinesterases in vitro. Both horse-serum and rat-brain cholinesterases were protected against the above inhibitors. It is thought that the basis of the protection is a reaction between catechol and the inhibitor. 

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]. 

Some biologically important o-quinones can react with the superoxide ion giving catechol derivatives, which may play a role in many diseases. For example, compounds bearing a nitro-catechol moiety have been claimed to be efficient catechol-0-methyl transferase inhibitors (Suzuki et al. 1992, Perez et al. 1992). The transferase is the first enzyme in the metabolism of catecholamine a hyperactivity of this enzyme leads to Parkinson s disease. Therefore, prediction of biological activity and antioxidant properties of quinones is an important challenge for researchers. 

Flecht SS, Carmella S, Furuya K, et al Polynuclear aromatic hydrocarbons and catechol derivatives as potential factors in digestive tract carcinogenesis. Environ Mutagens Car-cinog Proc Int Conf 5M-556, 1982... 

O4AICIN2C34H54, Aluminum, dimethanol-1,2-bis(2-hydroxy-3,5-bis(tert-butyl)benzylide-neimino)ethane-, chloride, 34 17 O4BM0N6C16H17, Molybdenum(II), dicarbonyl hydridotris( 1 -py razolyl)borato 7)-(1,2,3)-(+)-( 1 R,2R)-1 -(methoxycarbonyl)-2-propen-l-yl -, 34 105 O4B2C12H4, Diborane(4), catechol derivative, 34 4... 

The intense, for the Siberian beaver leathery, odor of castoreum is caused largely by phenolic compounds (e.g., 4-alkylphenols and catechol derivatives [256]), which beavers take in with their food and excrete into their abdominal pouch. Castoreum was used mainly in fine fragrances for its characteristic, long-lasting odor, particularly for delicate leather nuances. FCT 1973 (11) p. 1061 [8023-83-4], [92704-04-6], [92704-05-7]. 

Some regulatory mechanisms have been revealed for the TPHs, such as activation by phosphorylation-dependent interaction with 14-3-3 proteins (71,72). Catecholamines are also reported to be inhibitors of TPH (73). l-DOPA and L-DOPA-quinone derivatives, but not the end product serotonin, have also been shown to be inhibitors of TPH activity (see Martinez et al. 2001 (74) for the physiological and pharmacological implications of the inhibitory effects by catechol derivatives). 

Phenylephrine was discussed previously when describing the actions of a relatively pure 04 agonist (Table 9-2). Because it is not a catechol derivative (Figure 9-4), it is not inactivated by COMT and has a longer duration of action than the catecholamines. It is an effective mydriatic and decongestant and can be used to raise the blood pressure (Figure 9-6). 

---