Oxidative chemistry of the natural antioxidant hydroxytyrosol:: hydrogen peroxide-dependent hydroxylation and hydroxyquinone/o-quinone coupling pathways

Oxidation of the natural antioxidant hydroxytyrosol (1) with peroxiclase/H2O2 in phosphate buffer at pH 7.4 led to the formation of two main ethyl acetate-extractable products. These could be isolated by preparative TLC after reduction and acetylation, and were identified as the tetraacetyl derivative of 2-(2,4,5-trihydroxypheniyl)ethanol (3) and the heptaacetyl derivative of the pentahydroxybiphenyl 4 by 2D NMR and NIS analysis. Similar oxidation of 4-methylcatechol gave. after the same work-up, the acetylated derivatives of 1,2,4-trihydroxy-5-methylbenzene (5) and the pentahydroxybiphenyl 6. Mechanistic experiments Suggested that hydrogen peroxide affects the course of the oxidation of 1 by adding to the first formed o-quinone to give a hydroxyquinone intermediate. This could bring nucleophilic attack to the o-quinone of I to give the dimer 4. These results disclose novel oxidative pathways of 4-alkylcatechols and provide an improved chemical basis to enquire into the mechanism of the antioxidant action of 1. (c) 2005 Elsevier Ltd. All rights reserved.