title: Two Potent OXE-R Antagonists: Assignment of Stereochemistry.
abstract: 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is formed by the oxidation of 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE), which is a major metabolite of enzymatic oxidation of arachidonic acid (AA). 5-Oxo-ETE is the most potent lipid chemoattractant for human eosinophils. Its actions are mediated by the selective OXE receptor, which is therefore an attractive target in eosinophilic diseases such as allergic rhinitis and asthma. Recently, we have reported two excellent OXE receptor antagonists that have IC50 values at low nanomolar concentrations. Each of these antagonists has a chiral center, and the isolation of the individual enantiomers by chiral high-performance liquid chromatography (HPLC) revealed that in each case one enantiomer is over 300 times more potent than the other. To unambiguously assign the stereochemistry of these enantiomers and to provide access to larger amounts of the active compounds for biological testing, we report here their total synthesis.
authors: Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology , 150 West University Boulevard, Melbourne, Florida 32901, United States.
authors: Pranav
authors: P
authors: Patel
authors: Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology , 150 West University Boulevard, Melbourne, Florida 32901, United States.
authors: Chintam Nagendra
authors: CN
authors: Reddy
authors: Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology , 150 West University Boulevard, Melbourne, Florida 32901, United States.
authors: Vivek
authors: V
authors: Gore
authors: Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology , 150 West University Boulevard, Melbourne, Florida 32901, United States.
authors: Shishir
authors: S
authors: Chourey
authors: Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology , 150 West University Boulevard, Melbourne, Florida 32901, United States.
authors: Qiuji
authors: Q
authors: Ye
authors: Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology , 150 West University Boulevard, Melbourne, Florida 32901, United States.
authors: Yannick P
authors: YP
authors: Ouedraogo
authors: Meakins-Christie Laboratories, Department of Medicine, McGill University , 3626 St. Urbain Street, Montreal, Quebec H2X 2P2, Canada.
authors: Sylvie
authors: S
authors: Gravel
authors: Meakins-Christie Laboratories, Department of Medicine, McGill University , 3626 St. Urbain Street, Montreal, Quebec H2X 2P2, Canada.
authors: William S
authors: WS
authors: Powell
authors: Claude Pepper Institute and Department of Chemistry, Florida Institute of Technology , 150 West University Boulevard, Melbourne, Florida 32901, United States.
authors: Joshua
authors: J
authors: Rokach
keywords: 5-Oxo-ETE; OXE receptor; antagonist; chiral auxiliary; enantiomeric; eosinophil; optical purity