title: Regenerable antioxidants-introduction of chalcogen substituents into tocopherols.
abstract: To improve the radical-trapping capacity of the natural antioxidants, alkylthio-, alkylseleno-, and alkyltelluro groups were introduced into all vacant aromatic positions in β-, γ- and δ-tocopherol. Reaction of the tocopherols with electrophilic chalcogen reagents generated by persulfate oxidation of dialkyl dichalcogenides provided convenient but low-yielding access to many sulfur and selenium derivatives, but failed in the case of tellurium. An approach based on lithiation of the appropriate bromo-tocopherol, insertion of chalcogen into the carbon-lithium bond, air-oxidation to a dichalcogenide, and final borohydride reduction/alkylation turned out to be generally applicable to the synthesis of all chalcogen derivatives. Whereas alkylthio- and alkylseleno analogues were generally poorer quenchers of lipid peroxyl radicals than the corresponding parents, all tellurium compounds showed a substantially improved radical-trapping activity. Introduction of alkyltelluro groups into the tocopherol scaffold also caused a dramatic increase in the regenerability of the antioxidant. In a two-phase lipid peroxidation system containing N-acetylcysteine as a water-soluble co-antioxidant the inhibition time was up to six-fold higher than that recorded for the natural antioxidants.
authors.affiliation: Department of Chemistry - BMC, Uppsala University, Box-576, 751 23 Uppsala (Sweden).
authors.forename: Jia-Fei
authors.initials: JF
authors.lastname: Poon
authors.forename: Vijay P
authors.initials: VP
authors.lastname: Singh
authors.forename: Jiajie
authors.initials: J
authors.lastname: Yan
authors.forename: Lars
authors.initials: L
authors.lastname: Engman
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry*; D018011:Chalcogens / Q000737:chemistry*; D015227:Lipid Peroxidation; D010084:Oxidation-Reduction; D012643:Selenium / Q000737:chemistry; D013691:Tellurium / Q000737:chemistry; D024505:Tocopherols / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D018011:Chalcogens; D012643:Selenium; D013691:Tellurium; D024505:Tocopherols; D000111:Acetylcysteine
keywords: antioxidant; chain-breaking activity; organotellurium; regenerable; tocopherol