Chiral Analogs of a-tocopherol. Antioxidant Activity of the (R) and (S) Enantiomers of {2-[6-hydroxy-2,5,7,8-tetramethylchroman-2-yl]ethyl}-trimethylammonium-p-toluenesulfonate Depending on Their Configuration

Abstract

Starting with the (R) and (S) enantiomers of 2-(6-benzyloxy-2,5,7,8-tetramethylchroman-2-yl)ethanol, prepared previously by partial acylation of the corresponding racemic alcohol in the presence of the most easily available lipase, from the yeast Candida cylindracea, a four-stage syntheses was developed for both enantiomers of {2-[6-hydroxy-2,5,7,8-tetramethylchroman-2-yl]ethyl}trimethylammonium p-toluenesulfonate (MDL-73404), which are chiral analogs of α-tocopherol. Comparative biomedical testing of samples of MDL-73404 salts with different enantiomer compositions in relation to their effects on the generation of reactive oxygen species by peritoneal macrophages from white rats in systems containing luminol or lucigenin demonstrated different levels of inhibition of spontaneous and 12-O-myristyl-13-O-acetylphorbol-activated macrophage chemiluminescence.