Phosphorylated disaccharides

The benzyl and phenyl groups were removed by hydro-genolysis over palladium and platinum catalysts, respectively, and the acetyl groups by treatment with ammonia in methanol. In this case too, the monoammonium salt of the phosphorylated disaccharide 2 was isolated physical and chemical parameters of the compounds obtained by both methods were identical. 

The phosphorylated disaccharide is now transferred from its lipid carrier to a growing chain of teichoic acid, elongating it by one repeating unit and releasing a lipid phosphate. This can now act as an acceptor again, so starting a new cycle. 

Leishmaniasis is a disease that affects over 12 million people worldwide. One of the carbohydrates that is exposed on the Leishmania parasite surface is a structure consisting of a glycosylphosphatidylinositol (GPl) anchor, a repeating phosphorylated disaccharide and tetrasaccharide cap 14. The tetrasaccharide cap was synthesized by automation [38] using three building blocks (Scheme 9). 

Trehalose 6-phosphate has been prepared in 28% yield through unimolar phosphorylation of the disaccharide with diphenyl phos-... 

The structural components encountered in E. coli are also present in lipid A of other bacterial sources. Thus, a survey of the structures analyzed shows that lipid A, in general, contain two g/wcoconfigured and pyranosidic D-hexosamine residues (2-amino-2-deoxy-D-glucose, GlcpN, or 2,3-diamino-2,3-dideoxy-D-glucose, GlcpN3N, also termed DAG (49,50)], which are present as a ) -(l — 6)-linked disaccharide (monosaccharide backbones have also been identified, but the respective lipid A lack endotoxic activity). The disaccharide is phosphorylated by one or, in most cases, two phosphate... 

Figure 14.7 Models of phosphorylated high-mannose M7 and a glycopeptide mimic obtained by MD calculation showing similar conformations. They are seen from the point of interaction with the mannose-6-phosphate receptor. Disaccharide phosphates are emphasized as spheres.76...

Fructose is found in honey and fruit and as part of the disaccharide sucrose (common table sugar). Sucrose is hydrolyzed by intestinal brush border sucrase, and the resulting monosaccharides, glucose and fructose, are absorbed into the portal blood. The liver phosphorylates frurtose and cleaves it into glyceraldehyde and DHAP. Smaller amounts are metabolized in renal proximal tubules. The pathway is shown in Figure 1-12-7 important enzymes to remember are ... 

Systematic investigations of mannose-binding proteins with clustered mannosides other than natural multiantennary oligosaccharides have been rather scarce until recently. However, using 6 -0-phosphorylated mannose disaccharide scaffolded on peptide templates using combinatorial glycopeptide libraries. 

D-Galactose, a product of hydrolysis of the disaccharide lactose (milk sugar), passes in the blood from the intestine to the liver, where it is first phosphorylated at C-l, at the expense of ATP, by the enzyme galactokinase ... 

As discussed above, one of the two phosphoryl groups present in lipid A is linked to the glycosidic hydroxyl group of the reducing glucosamine residue in the disaccharide. The location of the second phosphoryl residue was identified in the following way... 

The structural principle identified in many lipid A s as the hydrophilic backbone, a phosphorylated B(1— 6)-linked D-glucosa-minyl disaccharide, is present in closely related and taxonomi-cally remote groups of bacteria. Therefore it represents an ubiquitous and common component of lipid A s from various Gram-negative bacteria. A D-glucosaminyl disaccharide being B(1— 6)-linked has, to our knowledge, not been found in other natural substances. Hence, this structure is unique and characteristic for Lipid A. 

The next step of our synthetic study was the preparation of 1- and/or 4 -phosphates of the acyl disaccharide because it seemed to be important to have both the 1- and 4 -monophosphates and the 1,4 -diphosphate in order to know the role of both phosphate moieties for activities. Though we first attempted the direct and simultaneous phosphorylation of the 1- and 4 -hydroxyl groups in Q, this could not be achieved under various conditions. The two phosphate moieties were therefore introduced separately, using different procedures (4). 

In this manner, we now succeeded to phosphorylate both free hydroxyl groups on C-l and C-4 directly and simultaneously even in the presence of 3-hydroxyacyl moieties on the 2-amino groups of the disaccharide. This was, as already described, not possible by combination of the known procedures. 

Compound 6-Pre closely resembles the intermediates used by Kusumoto jet al. ([this volume) and by van Boeckel et al. (16) for the preparation of disaccharide oxazolines, which were then elaborated into fully phosphorylated analogs (1,4 -diphosphates). In a formal sense, therefore, the synthesis of 6-Pw effectively constitutes a synthesis, by our revised route, or the 1,4 -bisphosphate having palmitoyl groups at positions 2, 3, 2, and 6. An additional palmitoyl group could be attached at position 4 if desired. 

---