Regenerable Antioxidants-Introduction of Chalcogen Substituents into Tocopherols

• Published in: Chemistry : a European journal 2015-02, Vol.21 (6), p.2447-2457
• Main Authors: Poon, Jia-fei, Singh, Vijay P., Yan, Jiajie, Engman, Lars
• Format: Article
• Language: English
• Subjects: Acetylcysteine - chemistry; antioxidant; Antioxidants; Antioxidants - chemistry; chain-breaking activity; Chalcogens - chemistry; Chemistry; Derivatives; Inhibition; Insertion; Lipid Peroxidation; Lipids; organotellurium; Oxidation; Oxidation-Reduction; Parents; regenerable; Selenium; Selenium - chemistry; Tellurium - chemistry; Tocopherol; Tocopherols - chemical synthesis; Tocopherols - chemistry; Vitamin E
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.201405895

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. In an effort to improve on nature, chalcogen substituents were introduced into all vacant aromatic positions in β‐, γ‐, and δ‐tocopherol (see scheme). The alkyltelluro‐substituted compounds were significantly better radical‐trapping agents than the parents and the corresponding S and Se derivatives. By using N‐acetylcysteine as a co‐antioxidant, the inhibition time was six‐fold longer than that recorded for the natural antioxidants.