Salicylate hydroxylation

Blackburn AC, Doe WF, Buffinton GD (1998) Salicylate hydroxylation as an indicator of OH radical generation in dextran sulfate-induced colitis. Free Rad Biol Med 25 305-313 Bonifacic M, Stefanic I, Hug GL, Armstrong DA, Asmus K-D (1998) Glycine decarboxylation The free radical mechanism. J Am Chem Soc 120 9930-9940 Bonifacic M, Armstrong DA, Stefanic I, Asmus K-D (2003) Kinetic isotope effect for hydrogen abstraction by OH radicals from normal and carbon-deuterated ethyl alcohol in aqueous solution. J Phys Chem B 107 7268-7276... 

Coudray C, Talla M, Martin S, Fatome M, Favier A (1995) FIPLC-electrochemical determination of salicylate hydroxylation products as an in vivo marker of oxidative stress. Anal Biochem 227 101-111... 

Ghiselli A, Laurenti O.deMattiaG, Maiani G, Ferro-Luzzi A (1992) Salicylate hydroxylation as an early marker of in vivo oxidative stress in diabetic patients. Free Rad Biol Med 13 621-626... 

The ability of so-called hydroxyl radical scavengers such as mannitol, ethanol, and dimethyl sulfoxide to inhibit reactions such as salicylate hydroxylation has been used as supporting evidence not only for hydroxyl radical... 

Salicylate esters derived from a three-step approach involving salicylic acid, 2-iodophenol, and but-3-en-2-ols undergo further iridium(I)-catalyzed intramolecular oxyacylation of the alkene moiety using the salicylate hydroxyl as directing group to afford 2,2-disubstituted chromans (Scheme 25) (14JOC11383). 

The best known aryl ester is O acetylsalicylic acid better known as aspirin It is pre pared by acetylation of the phenolic hydroxyl group of salicylic acid... 

A seemingly complex heterocycle which on close examination is in fact a latentiated derivative of a salicylic acid shows antiinflammatory activity. It might be speculated that this compound could quite easily undergo metabolic transformation to a salicylate and that this product is in fact the active drug. Condensation of acid 134 with hydroxyl amine leads to the hydroxamic acid 135. Reaction of... 

The esterification of the phenolic hydroxyl group in salicylic acid with acetic acid results not only in an... 

Hydroxybenzoates can nndergo hydroxylation with or withont concomitant loss of CO2. For example, salicylate —> catechol + CO2 (salicylate-l-hydroxylase) (Fignre 3.9a) (White-Stevens et al. 1972) and 4-hydroxybenzoate —> 1,4-dihydroxybenzene + CO2 [(4-hydroxy-benzoate 1-hydroxylase (decarboxylating)] in Candida parapsilosis (Fignre 3.9b) (Eppink etal. 1997). 

White-Stevens RH, H Kamin (1972) Studies of a flavoprotein, salicylate hydroxylase. I. Preparation, properties, and the uncoupling of oxygen reduction from hydroxylation. J Biol Chem 247 2358-2370. 

The degradation of salicylate to catechol is initiated by monooxygenation accompanied by decarboxylation (salicylate-l-hydroxylase), and two different and independent salicylate hydroxylases have been found in the naphthalene-degrading Pseudomonas stutzeri ANIO (Bosch et al. 1999). Alternatively, in Rhodococcus sp. strain B4, salicylate is hydroxylated to 2,5-dihydroxybenzoate by salicylate-5-hydroxylase (Grand et al. 1992). An alternative occurs for 5-hydroxy- and 5-aminosalicylate in Pseudaminobacter salicylatoxidans in which ring fission is accomplished directly (Hintner et al. 2001). 

Grootveld, M. and Halliwell, B. (1986b). Aromatic hydroxyla-tion as a potential measure of hydroxyl radical formation in vivo. Identification of hydroxylated derivatives of salicylate in human body fluids. Biochem. J. 237, 499-504. 

Giovanni, A., Liang, L.R, Hastings, T.G., Zigmond, M.J. Estimating hydroxyl radical content in rat brain using systemic and intraventricular salicylate impact of methamphetamine. J. Neurochem. 64 1819, 1995. 

C=0) is linked to both an alkyl group (or hydrogen atom) and a hydroxyl group. The medicinal activity of salicylic acid suggests that it is this phenolic precursor (phenol, Fig. 13.4.3), not acetylsalicylic acid (Fig. 13.4.4), that is the prime pain... 

Decomposition of salicin (2-(hydroxymethyl)phenyl-/ -D-glucopyranoside) yields two alcohols glucose (a compound with numerous 1°, 2°, and a 3° hydroxyl functionalities, Fig. 13.4.6) and l-0H-2-CH20H-benzene (a 1° alcohol, Fig. 13.4.7). Further oxidation of l-0H-2-CH20H-benzene leads to the formation of salicylic acid ... 

Replacement of the hydroxyl group on the phenyl ring with a carboxyl group forms a molecule of benzoic acid. Addition of a hydroxyl at the 2-position on a benzoic acid molecule forms 2-hydroxybenzoic acid or salicylic acid. The slightly more complex phenylpropanoid skeleton contains a linear three-carbon chain (the propanoic group) added to the benzene ring (the phenyl group). Addition of ammonia to carbon 2 of this three-carbon side chain yields the amino acid phenylalanine (Fig. 3.3). Phenylalanine... 

Now, we will consider the major reactions of peroxynitrite with biomolecules. It was found that peroxynitrite reacts with many biomolecules belonging to various chemical classes, with the bimolecular rate constants from 10-3 to 10s 1 mol 1 s 1 (Table 21.2). Reactions of peroxynitrite with phenols were studied most thoroughly due to the important role of peroxynitrite in the in vivo nitration and oxidation of free tyrosine and tyrosine residues in proteins. In 1992, Beckman et al. [112] have showed that peroxynitrite efficiently nitrates 4-hydroxyphenylacetate at pH 7.5. van der Vliet et al. [113] found that the reactions of peroxynitrite with tyrosine and phenylalanine resulted in the formation of both hydroxylated and nitrated products. In authors opinion the formation of these products was mediated by N02 and HO radicals. Studying peroxynitrite reactions with phenol, tyrosine, and salicylate, Ramezanian et al. [114] showed that these reactions are of first-order in peroxynitrite and zero-order in phenolic compounds. These authors supposed that there should be two different intermediates responsible for the nitration and hydroxylation of phenols but rejected the most probable proposal that these intermediates should be NO2 and HO. ... 

Subsequent studies confirmed that there is no reliable evidence of the MPO-catalyzed hydroxyl generation by neutrophils [235,236]. Kettle and Winterbourn [237] demonstrated that the hydroxylation of salicylate by stimulated neutrophils or the purified MPO, which yielded 2,5-dihydroxybenzoate, was unaffected by hydroxyl radical scavengers mannitol or DMSO. These authors suggested that an active peroxidative agent in this system was the reduced Compound III, formed by the following reactions ... 

---