Synthesis of vitamin E analogues: Possible active forms of vitamin E

We synthesized several vitamin E analogues containing oxygenated functional groups in place of the 8-methyl group which is common to all the natural vitamin E congeners, based on the hypothesis that the methyl group might be metabolically oxidized to produce active forms which might have specific functions other than the antioxidant function. All the vitamin E analogues examined had antioxidant activity. 8-[6-Hydroxy-2,5,7-trimethyl-2(4,8,12-trimethyltridecanyl)chroman]meth anol (1d) and 2,5,7-trimethyl-2-(4,8,12-trimethyltridecanyl)chroman-6-ol (4d) showed similar activity to α-tocopherol. 6-Hydroxy-2,5,7-trimethyl-2(4,8,12-trimethyltridecanyl)chroman-8-carba ldehyde (2d) and 6-hydroxy-2,5,7-trimethyl-2-(4,8,12-trimethyltridecanyl)chroman-8-carb oxylic acid (3d) showed weaker activity than α-tocopherol, but their duration of action, especially that of 3d was considerably longer.