Protection of catechols

Cren-Olive C, Lebrun S, Rolando C. An efficient synthesis of all mono and tri-O-methylated analogues of (+)-catechin including the major metabolites through sequential protection of catechol ring. J Chem Soc Perkin Trans 1 2002 6 821-830. Cren-Olive C. Synthese, Physico-Chimie et Analyse de Flavan-3-ols. Ph.D. dissertation, Universite des Sciences et Technologies de Lille, Lille, 2001. 

Catechol derivatives, because of the vicinal relationship of the two ortAo-hydroxy groups, may also be blocked by the appropriate use of a number of bidentate groups in addition to those shown in Table 4.1 (Table 4.2). Borate esters are frequently employed not only in the protection of catechol groupings, but also pen -dihydroxy groupings in naphthalene derivatives and chelated hydroxycarbonyl systems in aromatic nuclei. 

See also E. Haslam, Protection of Phenols and Catechols, in Protective Groups in Organic Chemistry, J. F. W. McOmie, Ed., Plenum Press, New York and London, 1973. pp. 145-182. 

A cyclic borate can be used to protect a catechol group during base-catalyzed alkylation or acylation of an isolated phenol group the borate ester is then readily hydrolyzed by dilute acid. ... 

Pedersen reasoned that there must have been a small amount of catechol present which had not been protected properly. This must have led to the formation of 1 in situ... 

Commercial PCP preparations often contain variable amounts of chlorophenols, hexachloroben-zene, phenoxyphenols, dioxins, dibenzofurans, chlorinated diphenyl ethers, dihydroxybiphenyls, anisoles, catechols, and other chlorinated dibenzodioxin and dibenzofuran isomers. These contaminants contribute to the toxicity of PCP — sometimes significantly — although the full extent of their interactions with PCP and with each other in PCP formulations are unknown. Unless these contaminants are removed or sharply reduced in existing technical- and commercial-grade PCP formulations, efforts to establish sound PCP criteria for protection of natural resources may be hindered. 

It is interesting to underline that there is another (plant) enzyme which possesses a coordinatively similar dicopper environment catechol oxidase.11 As already mentioned in Chapter 6, Section 3, such an ubiquitous enzyme catalyses the two-electron oxidation by molecular dioxygen of catechols to the corresponding quinones (the so-generated quinones in turn polymerize to form brown polyphenolic catechol melanins, which protect damaged plants from pathogens or insects). 

The preparation of dibenzo-18-crown-6 polyether directly from catechol and bis(2-chloroethyl) ether has been reported previously. The present procedure is an improvement of this method. Although dibenzo-18-crown-6 polyether can be obtained in 80% yield from bis-[2-(o-hydroxyphenoxy)-ethyl] ether and bis(2-chloroethyl) ether, the former intermediate has to be synthesized by a method involving several steps. One of the hydroxyl groups of catechol must be protected against alkali by reaction with a molecule of dihydropyran or chloromethylm ethyl ether. Then the intermediate is treated with bis(2-chloroethyl) ether in the presence of alkali and, finally, converted into the desired intermediate by acid hydrolysis. The yield of bis[2-(o-hydroxyphenoxy)-ethyl] ether was less than 40% so that the overall yield of dibenzo-18-crown-6 polyether never approached 39-48%, the yield of the present direct method. 

Carboxylic acids, protection of, 224-276 as amides and hydrazides, 270-276 as esters, 227-270 Reactivity Chart 6, 433-436 S-Carboxymethyl thioethers, to protect thiophenols, 294-295 Catechols, protection of, 170-174 as cyclic acetals and ketals, 170-172 as cyclic esters, 173-174 Reactivity Chart 4, 425-428 CBZ, see Benzyl carbamates Chloroacetamides, to protect amines, 352-353... 

N-Salicylideneamines, to protect amines, 370 Selective cleavage, 411-412 of benzyl carbamates, 339-340 of benzyl ethers, 49-56 of catechol protective groups, 171 of N- vs. 5-dimethylphosphinothioyl groups, 307... 

Protection of a catechol as its diphenylmethylene acetal also featured in a synthesis of the Galanthamine alkaloids.182 Here, the deprotection reaction was accomplished using trifluoroacetic acid — conditions that also effected protonolysis of the aryl silane [Scheme 3.98]. 

These pyrones undergo Diels-Alder reactions with electron-deficient alkenes with loss of COj and formation of an aromatic ring. Thus reaction with 1,1-dimethoxyethylene (11, 279-281) provides a regiospecific route to methyl salicylates (e.g., 3), which are convertible in several steps into catechol derivatives (4) or by decarbomethoxylation into phenol ethers (5). Similar reactions with vinylene carbonate or 1, 1,2-trimethoxyethylene provide regiospecific routes to phenols, differentially protected derivatives of catechol, resorcinol, or pyrogallol (equation II). 

There are two catecholate siderophores which may be chosen as model compounds for synthesis the cyclic enterobactin and the linear parabactin precursor N. N8-bis(2,3-dihydroxybenzoyl)spermidine. Both of these natural products are capable of the rapid removal of iron from transferrin, the human iron transport protein 89-90). The synthesis of these and other catecholate ligands routinely requires protection of the phenolic oxygens (for example, by methyl, benzyl or acetyl groups). Very few preparations of catechol-containing siderophores have appeared in which the unprotected 2,3-dihydroxybenzoyl group is used in the synthesis 91,92). 

Salama, S.A., Kamel, M., Awad, M., Nasser, A.H., Al-Hendy, A., Botting, S., and Arrastia, C. (2008) Catecholestrogens induce oxidative stress and malignant transformation in human endometrial glandular cells protective effect of catechol- O-methyltransferase. 

Various substituted and unsubstituted methylenedioxy derivatives of apomorphine and V-n-propylnorapomorphine have been studied by Baldessarini et and one of these, 10,11 -methylenedioxy-V-n-propylnorapomorphine, was found to be both a long-acting and an orally efficient prodrug (Fig. 33.28). The oral activity of the compound can be ascribed to the protection of the catechol system from the first-pass effects by the methylenedioxy group. The conversion to the free catechol is possible thanks to the hepatic microsomal enzymes (see Chapters 28 and 29 on drug metabolism). 

Figure 1. Protection by catechol against H2O2 inactivation of metapyrocatechase...

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