A convenient synthesis of 2-deoxy-2-[(R)-1-hydroxytetradecanamido]-3-O-[(R)-3-hydroxytetradecanoyl]-α-d-glucopyranose 1-phosphate (lipid X)

Immunostimulatory, but not antiendotoxin, activity of lipid X is due to small amounts of contaminating N,O-acylated disaccharide-1-phosphate: in vitro and in vivo reevaluation of the biological activity of synthetic lipid X

“…These findings support the work of Lasfargues and Chaby (19) and of Birkland et al (2), who found that, in contrast to reports in the literature (15,28,35), apparently uncontaminated lipid X was inactive as an in vitro inducer of TNF or as a stimulator of nonspecific host resistance (18). Together, these data strongly suggest that earlier results obtained with synthetic lipid X of unspecified purity could have been influenced considerably by contam-inants that formed during synthesis by previously published procedures (16,24).…”

“…It was shown recently that synthetic lipid X (24) can be contaminated with N,O-acylated disaccharide-i-phosphate, which can form during the last step of its synthesis (1). It is likely that the biological activities of some batches of lipid X, either of synthetic or of bacterial origin, were influenced by small amounts of immunostimulatory contaminants.…”

“…LPS was a phenol water extract of Salmonella abortus-equi (Sigma Chemical Co., St. Louis, Mo.). Lipid X was synthesized from D-glucose as previously described (24). Contaminated lipid X (designated batch A) was pure with respect to the spectroscopic and microanalysis data.…”

Multi-dimensional NMR structural analyses of purified Lipid X and Lipid A (endotoxin)

“…The resultant NMR assignments for natural Lipid X are summarized in Table 1 and compared with those reported for synthetic Lipid X. 35 The 2D HMQC 1 H-13 C correlation map of Lipid A is shown in Fig. 8 of the four hydroxymyristates are resolved in the HMQC map (Fig.…”

SDZ MRL 953, a novel immunostimulatory monosaccharidic lipid A analog with an improved therapeutic window in experimental sepsis

“…The elucidation of the correct structure of lipid A (8,26) and the subsequent success in the total synthesis of biologically active lipid A and analogs (9)(10)(11)(12)27) have rekindled interest in the possibility of separating the immunostimulatory and toxic moieties of endotoxin. Efforts to identify beneficial immunostimulatory lipid A derivatives have concentrated on synthetic analogs representing both the nonreducing (10)(11)(12) and reducing sugar moieties, such as lipids X and Y (15,27). Synthetic lipid A subunits of the nonreducing sugar moiety such as GLA-27 and GLA-60 were reported to activate B cells and macrophages and to induce release of mediators including gamma interferon and tumor necrosis factor (TNF) at nontoxic doses (for a review, see reference 5).…”