C-D-glucopyranosyl derivatives of tocopherols - Synthesis and evaluation as amphiphilic antioxidants

Treatment of dimethylhydroquinone dimethyl ethers (ortho and meta isomers) with glycopyranose pentaacetates (D-gluco, D-galacto) in the presence of SnCl₄ and F₃CCO₂Ag selectively afforded the corresponding C-β-D-glycosyl derivatives by aromatic electrophilic substitution. Oxidation of the dimethoxybenzene moiety with ceric ammonium nitrate delivered C-β-D-glycosyl-dimethylbenzoquinones, which were reduced with Na₂S₂O₄ to the corresponding C-β-D-glycosyldimethylhydroquinones. ZnCl₂-catalyzed cyclization either with methylbut-2-en-1-ol (prenyl alcohol) or with all-racemic phytol led to acetyl-protected C-β-D-glycosyl chromanols or C-β-D-glycosyl tocopherols, the sugar residues of which were deacetylated under base catalysis conditions. These new molecules were evaluated as antioxidants in terms of their ability to inhibit the peroxidation of linoleic acid in SDS micelles. The position of the C-glucosyl moiety on the phenolic nucleus emerges as the critical structural determinant of their activity.