Lipid A, a biologically active constituent of LPS of Gram-negative bacteria, was found recently to contain a β-1,6-linked D-glucosamine disaccharide substituted by two phosphates and four ester- and amide-bonded fatty acids. On the basis of these results, we report here new syntheses of Lipid X,Y and Salmonella mutant Lipid A. 1) Synthesis of Lipid X Our methodology includes new development of selective removal of the N-acyl group from the acid-unstable 4,6-isopropylidene compound (3) leading to the novel key-compound (4), whose one amino and four hydroxyl groups can be chemically distinguishable from each other and easily convertible into the required substituents for Lipid A and the related compounds. Successful conversion of 4 into Lipid X was realized as shown in Scheme 1. 2) Synthesis of Lipid Y A new chemoselective debenzylation of the glycosidic benzyl group of the glucosamine derivative (13) was developed and applied to the synthesis of Lipid Y as described in Scheme 2. 3) Synthesis of Salmonella mutant Lipid A New development of the common key disaccharide intermediate (26) bearing chemoselected two amino and six hydroxyl groups which is capable of direct conversion into several Lipids A and a formal synthesis of Salmonella mutant Lipid A from 26 were realized as indicated in Scheme 3.
