Synthesis of 5-(Fluorophenyl)tocopherols as Novel Dioxin Receptor Antagonists

gamma-Tocopherol, a component of the essential nutrient mixture commonly designated as vitamin E, was chemically combined with differently substituted monofluoro- and difluorophenyl moieties to produce potential antagonists for the human aryl hydrocarbon receptor (AhR). 5-Iodo-gamma-tocopherol was a very reliable starting material for the Pd-catalyzed reaction with ( fluorophenyl) boronic acids (Suzuki coupling). The ortho- and meta-fluoro-substituted derivatives showed conformational isomerism due to restricted rotation around the interaromatic bond. This effect was investigated by NMR spectroscopy. Three of the derivatives showed very high potency in assays and are promising candidates for further testing.