Synthesis and Biological Activities of Lipid A Analogs Possessing (beta)-Glycosidic Linkage at 1-Position

New lipid A analogs having acidic groups (beta)-glycosidically linked at the 1-position were synthesized in order to investigate the structural requirement for immunostimulating and endotoxic activity of lipid A. The (beta)-(phosphonoxy)ethyl (PE) and carboxymethyl (CM) analogs of Escherichia coli type having six acyl groups and those of the biosynthetic precursor type having four acyl groups were synthesized via a divergent synthetic route. The E. coli type (beta)-(phosphonoxy)ethyl analog, which was previously reported to be not endotoxic, showed strong immunostimulating activity comparable to the natural-type (alpha)-analog. The acidic functional groups are concluded to be essential but their strict spatial arrangement is not required for expression of the biological activity.