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

Oxidn. of the natural antioxidant hydroxytyrosol (2-(3,4-dihydroxyphenyl)ethanol) with peroxidase/H2O2 in phosphate buffer at pH 7.4 led to the formation of two main Et acetate-extractable products. These could be isolated by preparative TLC after redn. and acetylation, and were identified as the tetraacetyl deriv. of 2-(2,4,5-trihydroxyphenyl)ethanol and the heptaacetyl deriv. of pentahydroxybiphenyl by 2D NMR and MS anal. Similar oxidn. of 4-methylcatechol gave, after the same work-up, the acetylated derivs. of 1,2,4-trihydroxy-5-methylbenzene and pentahydroxybiphenyl. Mechanistic expts. suggested that hydrogen peroxide affects the course of the oxidn. of hydroxytyrosol by adding to the first formed o-quinone to give a hydroxyquinone intermediate. This could bring nucleophilic attack to the o-quinone of hydroxytyrosol to give the dimer. These results disclose novel oxidative pathways of 4-alkylcatechols and provide an improved chem. basis to enquire into the mechanism of the antioxidant action of hydroxytyrosol.