Recent developments in the organic synthesis of lipid A in relation to biologic activities

For elucidation of a relationship between chemical structure and biologic activity of lipid A, syntheses of 13 derivatives of glucosamine beta (1-6) disaccharide, which were acylated at 3, 4, and 6'-hydroxyl groups and/or phosphorylated at positions 1 and 4', were carried out. The results showed the importance of the presence of the phosphate group at either position 1 or 4' and of the beta-hydroxyl group in acyl function, particularly in N-linked fatty acids, for the exhibition of biologic activities characteristic of lipid A. New evidence on the positions of fatty acids in natural lipid A of Escherichia coli species obtained by means of 2D-H nuclear magnetic resonance was also demonstrated; the findings indicate that the 3'-hydroxyl group is acylated and the 6'-hydroxyl group in the molecule must be free.