Convenient synthesis of hydroxytyrosol and its lipophilic derivatives from tyrosol or homovanillyl alcohol.
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.
Bernini
Roberta
R
Dipartimento di Agrobiologia e Agrochimica, Università degli Studi della Tuscia, Via S. Camillo De Lellis snc, 01100 Viterbo, Italy. berninir@unitus.it
Mincione
Enrico
E
Barontini
Maurizio
M
Crisante
Fernanda
F
D002851:Chromatography, High Pressure Liquid; D004227:Dithionite / Q000737:chemistry; D004951:Esterification; D006719:Homovanillic Acid / Q000737:chemistry*; D006868:Hydrolysis; D007462:Iodobenzenes; D007463:Iodobenzoates / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D007462:Iodobenzenes; D007463:Iodobenzoates; C005975:3,4-dihydroxyphenylethanol; D004227:Dithionite; C011867:4-hydroxyphenylethanol; C476101:o-iodoxybenzoic acid; D010626:Phenylethyl Alcohol; D006719:Homovanillic Acid