Synthesis of lipid A analogues containing glucose instead of glucosamine and their LPS-antagonistic activities

Lipid A analogues containing glucose in substitution for glucosamine on the reducing end were synthesized, and the inhibitory activities on LPS-induced TNFα production (LPS-antagonistic activity) in vitro using human whole blood cells were measured. The IC50 values (nM) of these ten compounds, , , , , , , , , and , were 11.2, 15.4, 2.7, 0.1, 0.4, 1.3, 3.2, 3.2, 1.4 and 14.4, respectively. And also inhibitory activities (ID50) on TNFα production toward galactosamine loaded C3H/HeN mice in vivo of compounds , , , and were measured. The values of these compounds were 0.29, 0.50, 0.61, not dose-dependent and 0.33 mg/kg, respectively.