Synthesis and Antioxidant Profile of all-<i>r</i><i>ac</i>-α-Selenotocopherol

Abstract

all-rac-alpha-Selenotocopherol (6c) has been synthesized in 11 steps in 6.6% total yield. Key steps include chloromethylation to approach the persubstituted aromatic 9b and cyclization of alcohol precursor 10 by radical homolytic substitution at selenium to form the selenotocopherol heterocycle. Determination of the OH bond dissociation enthalpy (BDE) of 6c by electron paramagnetic resonance (EPR) equilibration techniques gave a value of 78.1 +/- 0.3 kcal mol(-1), approximately 1 kcal mol(-1) higher than that of alpha-tocopherol. Kinetic studies performed by measuring oxygen uptake of the induced oxidation of styrene in the presence of an antioxidant showed that selenotocopherol (6c) was a slightly poorer inhibitor than alpha-tocopherol, in agreement with the BDE values. In contrast to simpler selenotocopherol analogues, 6c was not regenerable in the presence of a stoichiometric coreductant in a two-phase lipid peroxidation model.