38 Synthesis of Fundamental Structure of Lipid A, the Active Principle in Endotoxin
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Liposaccharide component called "Lipid A" is a common structural unit of bacterial endotoxin, possessing most of the biological activities of endotoxin, e.g., lethal toxicity, pyrogenecity, adjuvant activity, antitumor effect and so on. Though the basic sturucture of lipid A has been recently established as 1, it exists in natural state as a mixture of congeners and analogs in fatty acid moieties and has never been obtained as a chemically pure substance. Therefore, synthetic approach to this lyposaccharide has been keenly requested particularly for the purpose of elucidation of the relationship between chemical structure and biological activity. We now describe the preparation of two acylated gulcosamine disaccharides 2 and 3 corresponding to the fundamental sturucture of Salmonella-type lipid A lacking phosphate moiety. While tetradecanoic acid was used for N- and O-acylations in 2, synthetic optically pure (R)-3-hydroxytetra-decanoic acid was employed for N-acylation in 3. Test of these synthetic liposaccharides for various biological activities of lipid A is now in progress.
