Disaccharides amide-linked

A. Le Chevalier, R. Pierre, S. Chambert, A. Doutheau, and Y. Queneau, Preparation of amide-linked pseudo-disaccharides by the carboxymethylglycoside lactone (CMGL) strategy, Tetrahedron Lett., 47 (2006) 2431-2434. 

Lipid A is the least variable component of LPS. It consists of a disaccharide of glucosamine, which is highly substituted with amide-linked and ester-linked long-chain fatty acids, each with a backbone of about 14 carbon atoms. Lipid A is responsible for the vast majority of both the harmful and the beneficial biological activities that have been attributed to endotoxin. A partial list of these activities is shown in Fig. 2. 

Figure 3.6 Structure of the Lipid A of Salmonella Species. The two glucosamine sugars are amide-linked at the 2-position to 3-OH fatty acids, which may themselves bear ester-linked fatty acids (R, Rg). Additional acylation by ester-linked 3-OH fatty acids may occur at 3 and 3 positions. The sugar 4-amino-arablnose may be substituted at the 4 of the glucosamine II and ethanolamlne at the 1 position of glucosamine I. The KDO disaccharide (not strictly part of lipid A) is attached to glucosamine II 6. The 4 position of glucosamine I is probably unsubstituted...

The condensation of hexuronic acid derivatives with hexosaminides to give amide-linked disaccharides is referred to in Chapter D-Galacturonic acid has been identified as a component of Pneumococcus type 25 capsular polysaccharide," and 2-O-methyl-D-glucuronic acid has been isolated for the first time in Nature from an extracellular polysaccharide of a species (Porphyridium cruentum) of red alga. The acidic sugar component in Klebsiella type 37 capsular polysaccharide has been identified as 4-0-[(5)-l-carboxyethyl]-D-glucuronic acid. Antibiotic substances and nucleosides that contain uronic acid components are referred to in Chapters 20 and 21, respectively. 

By use of pyrrolidine carbohydrate mimetics and a 6-aminoglucose or glucuronic add building block it was demonstrated that isomeric disaccharide mimetics can be prepared by formation of amide- and inverse amide-linked analogs such as 71 and 72 [59]. SPH 73 and several analogs with different uronic acid moieties... 

A second method uses permethylation of the dephosphated (48% aqueous HF, 48 h, 4°C) and 2H-reduced fipid A. This approach allowed the assignment of amide-bound fatty acids linked to GlcN(I) and GlcN(II), as well as the identification of the backbone structure as a HexpN disaccharide (85). Mass-spectrometric analysis of the products was performed by using either a short g.l.c. column (0.3 X 5 cm) or by direct insertion-probe analysis (87). In the case of C. violaceum (85), the mass spectra obtained from the permethyl-ated HexpN disaccharide bearing attached TV-methylacyl residues revealed unequivocally that both amino groups carried 12 0(3-OH). 

The general simplified structure of the LPS contains three domains (a) 0-polysaccharide chain, responsible for serot) e specificity, (b) core polysaccharide, a conserved, usually short oligosaccharide chain containing KDO and (c) lipid A, which is responsible for the toxicity and is composed of GlcNAc-disaccharide substituted by several fatty acids linked as esters or amides. 

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