REACTIONS OF THE VITAMIN-E MODEL-COMPOUND 2,2,5,7,8-PENTAMETHYLCHROMAN-6-OL WITH PEROXYL RADICALS

The vitamin E model compound 2,2,5,7,8-pentamethylchroman-6-ol (1b) was oxidized by peroxyl radicals generated by thermolysis of 2,2'-azobis(2,4-dimethylvaleronitrile) in oxygenated solvents. Oxidation of lb yielded 4a,5-epoxy-4a,5-dihydro-8a-hydroperoxy-2,2,5,7,8-pentamethylchroman-6(8aH)-one (5b), 7,8-epoxy-7,8-dihydro-8a-hydroperoxy-2,2,5,7,8-pentamethylchroman-6(8aH)-one (6b), 8a-[(2,4-dimethyl-1-nitrilopent-2-yl)dioxy]-2,2,5,7,8-pentamethylchroman-6(8aH)-one (3b), and a 5,5'-spirodimer product (7b). In otherwise identical reactions, yields of chromanone 3b and epoxides 5b/6b increased with increasing solvent polarity, whereas the yield of spirodimer 7b decreased. Deuterium substitution at C5a inhibited oxidation of 1b to spirodimer 7b and favored the formation of a novel 5,7'-spirodimer 11. The results demonstrate that the reaction medium controls the balance between competing reactions of chromanoxyl radical 2b and are consistent with the formation of epoxides and 8a-substituted tocopherones as the predominant products of a-tocopherol oxidation in biological membranes.