High-Yielding Synthesis of Methyl Orthoformate-Protected Hydroxytyrosol and Its Use in Preparation of Hydroxytyrosyl Acetate

The new methyl orthoformate of the powerful antioxidant hydroxytyrosol (or 2-(3,4-dihydroxyphenyl)ethanol) has been synthesized by a two-step high yielding procedure. The protection stabilizes hydroxytyrosol against autoxidation and allows both easy chromatographic purification and long term storage. The protective group is hydrolyzed over pH = 10 and below pH = 5, thus allowing the release of the active principle under physiological conditions. The use of the methyl orthoformate-protected hydroxytyrosol allows the preparation of protected hydroxytyrosyl esters, as the acetate here reported, by selective esterification of the alcoholic function. The subsequent quantitative deprotection under non-aqueous and mild conditions affords the hydroxytyrosyl acetate in high yields.