Convenient Synthesis of Hydroxytyrosol and Its Lipophilic Derivatives from Tyrosol or Homovanillyl Alcohol

Abstract

Hydroxytyrosol, a naturally occurred o-phenolic compound exhibiting antioxidant properties, was synthesized by a three-step high-yielding procedure from natural and low-cost compounds such as tyrosol or homovanillyl alcohol. First, the efficient chemoselective protection of the alcoholic group of these compounds was performed by using dimethyl carbonate (DMC) as reagent/solvent; second, the oxidation with 2-iodoxybenzoic acid (IBX) or Dess-Martin periodinane reagent (DMP) and in situ reduction with sodium dithionite (Na2S2O4) allowed the preparation of carboxymethylated hydroxytyrosol; finally, by a mild hydrolytic step, hydroxytyrosol was obtained in high yield and purity, as confirmed by NMR spectra and HPLC profile. By using a similar methodology, lipophilic hydroxytyrosol derivatives, utilized as additives in pharmaceutical, food, and cosmetic preparations, were prepared. In fact, at first the chemoselective protection of the alcoholic group of tyrosol and homovanillyl alcohol was performed by using acyl chlorides without any catalyst to obtain the corresponding lipophilic derivatives, and then these compounds were converted in good yield and high purity into the hydroxytyrosol derivatives by oxidative/reductive pathway with IBX or DMP and Na2S2O4.

A Straightforward Access to New Families of Lipophilic Polyphenols by Using Lipolytic Bacteria

“…However, despite of the many advances in organic synthesis during the last decades, the conventional chemical synthesis of mono acylated derivatives of polyphenols presents serious difficulties due to the high density of very similar functional groups, which requires extensive protection and deprotection sequences [10]. Thus, although some chemical approaches have been developed for accessing partially acylated polyphenols in a chemoselective way [11–13], most of such procedures are pure chemical synthesis, and involve the use of hazardous reagents or non-green conditions. As an alternative, the biotech industries have traditionally produced compounds of commercial interest by microbial fermentation, or by fermentation followed by subsequent chemical modification to improve specific properties, such as activity, solubility, absorption, pharmacokinetics or stability.…”

Sustainability, Innovation, and Green Chemistry in the Production and Valorization of Phenolic Extracts from Olea europaea L.

“…Hydroxytyrosol was synthesized in our laboratory as we have already described using a patented procedure [22,23].…”

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“…Later, the cathecolic function was inserted by a chemoand regio-selective reaction (Bernini et al 2008). An acrylic monomer containing Ty was synthesized and used for polymerization.…”