Structure and Synthesis of Biologically Active Bacterial Surface Substance, Lipid A

Abstract

Bacterial surface substance has been known to possess the endotoxic activity which is located at the lipid A part. Although a chemical structure for lipid A was early proposed, exact positions of fatty acids linked to the disaccharide skeleton have been ambiguous. We succeeded to obtain a chemically pure sample of natural E. coli mutant lipid A. From results obtained by 2 D-NMR analysis of this sample, we proposed a revised structure for lipid A. 2, 2'-N, 3, 3'-O-Tetraquis [(R) -3-hydroxytetradecanoyl] -β (1-6) -D-glucosamine disaccharide 1, 4'- diphosphate synthesized according to the proposed structure was quite identical with the natural acidic precursor of lipid A. This is the first achievement to establish the correct chemical structure of the natural lipid A by organic synthesis.