A Convenient Synthesis of Hydroxytyrosol Monosulfate Metabolites.

The growing interest in the bioactivity of natural polyphenols and of their metabolites requires metabolites to be used in bioassays and as standards in research protocols. We report here on the synthesis of several hydroxytyrosol metabolite monosulfates achieved using a simplified protocol with improved yields. A synthetic solution based on avoidance of high temperature conditions during the synthesis and of low pressure conditions during purification has been established. Monosulfates of several phenolic compounds, namely, hydroxytyrosol, hydroxytyrosol acetate, homovanillyl alcohol, homovanillyl alcohol acetate, homovanillic acid, ferulic acid, and 3,4-dihydroxyphenylethanoic acid, were efficiently synthesized in 1-2 steps in good yield and isolated using simple procedures. The proposed protocol was shown to be relatively rapid, efficient, cheap, and widely applicable to a number of catechol scaffolds.