Chemical Synthesis of a Biosynthetic Precursor of Lipid A with a Phosphorylated Tetraacyl Disaccharide Structure

Abstract

Abstract 2,2′-N:3,3′-O-Tetrakis[(R)-3-hydroxytetradecanoyl]-β(1-6)-d-glucosamine disaccharide 1,4′-bis(phosphate) and its dephospho derivatives were synthesized. The bisphosphate prepared was shown to be identical with a natural biosynthetic precursor of lipid A which corresponds to the lipophilic part of lipopolysaccharide (LPS) in bacterial cell wall. The synthetic bis- and monophosphates exhibited many of typical endotoxic activities of LPS. Consequently, this work established the chemical structure of the biosynthetic precursor of lipid A and elucidated the fundamental structure required for the expression of these activities.