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Synthesis of 5‐(Fluorophenyl)tocopherols as Novel Dioxin Receptor Antagonists
Author(s) -
Kloser Elisabeth,
Böhmdorfer Stefan,
Brecker Lothar,
Kählig Hanspeter,
Netscher Thomas,
Mereiter Kurt,
Rosenau Thomas
Publication year - 2011
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201100178
Subject(s) - chemistry , suzuki reaction , aryl , tocopherol , stereochemistry , nuclear magnetic resonance spectroscopy , aryl hydrocarbon receptor , combinatorial chemistry , vitamin e , organic chemistry , biochemistry , antioxidant , alkyl , transcription factor , gene
γ‐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‐γ‐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.