Synthesis of Tetrahydropyran-2-carboxylic Acid Derivatives of Lipid A Containing an Olefin in Their Chains and Their LPS-Antagonistic Activities

Abstract

Abstract Four tetrahydropyran-2-carboxylic acid derivatives with 3-(tetradec-7-enyloxy)tetradecyl chains instead of 3-(tetradecanoyloxy)tetradecanoyl chains in lipid A were synthesized and their biological activities toward human U937 cells, human whole blood cells and mouse peritoneal resident macrophages were measured. These compounds showed LPS-antagonistic activity toward these three kinds of cells. The IC50 values (nM) (1 M = 1 mol dm−3) of these four compounds (21, 21′, 24 and 24′) toward human monoblastic U937 cells were 2.2, 1.0, 0.017 and 0.055, respectively. However, the LPS-antagonistic activities (IC50 values) of these four compounds toward human whole blood cells were only 0.28, 0.21, 0.81 and 0.58 μM, respectively. The IC50 values (μM) toward mouse peritoneal resident macrophages were 2.49, 0.49, 0.91 and 0.69, respectively.