Monosaccharide precursors

Our strategy for synthesis of the oligosaccharide chains,27.28 calls for 2,6-dideoxyhexoses or the corresponding glycals to serve as precursors for both a- and p-glycosidation reactions. It a selective p-glycosidation protocol can be developed, then in principle any structural isomer or analogue of the natural product can be assembled from a common set of monosaccharide precursors.29... 

Mithramycin shows a completely P-linked chain of D-conflgurated saccharides. This requires a totally different approach for the synthesis which is also done by application of the DBE method. The previously obtained disaccharide 180 is P-glycosylated with the monosaccharide precursor 176 to give the trisaccharide 185. After reductive debromination (Bu3SnH), an acid deformylation deblocked the C-3" position which is oxidized with pyridinium dichromate. Nucleophilic attack at the carbonyl group by methyl lithium affords a 1 1.2 mixture of 186 and 187 none of which is the desired compound [93]. Obviously, the methyl branch is formed exclusively in the axial way. 

One of the primary dividends resulting from this disconnection was its exposure of a possible relationship between the target and a monosaccharide precursor. After systematic analysis, Pearson saw that the stereochemistry of 5 correlated perfectly with lactone 7. Furthermore, lactone 7 had a structure appropriate for easy synthetic elaboration into 6 since it was functionally differentiated at C(l) and C(4). It therefore appeared fully capable of being selectively modified in the manner required to obtain 5. 

Raetz, C.R.H. The enzymatic synthesis of lipid A Molecular structure and biologic function of monosaccharide precursors. Reviews of Infect Dis 6 (1984) 463. 

This strategy was mostly exploited by Sinay and his coworkers, enabling them to prepare various C-linked disaccharides in an expeditious fashion, via radical cyclization of temporarily tethered monosaccharidic precursors [111]. Medium-sized ring intermediates are obtained in reasonable yields, leading to the desired compounds after removal of the tether. The prototype of this approach is described below [112a] (O Scheme 52). 

Type 3 chain is the core disaccharide of glycoside glycoproteins, 16.8. The disaccharide serine (threonine) is the T antigen and its monosaccharide precursor the T antigen. ABH determinants are linked directly to the core disaccharide. They have been found, for example, in the gastric mucous membrane and in the glycoprotein of ovarian cysts. 

Saccharolipidsm, where fatty acids are linked in ester and amide linkages directly to sugar molecules. This is a relatively small class of molecules, best described in bacteria and plants. The most well known of these are the acylated glucosamine precursors of the lipid A component of the endotoxin thought to be responsible for the toxicity of Gram-negative bacteria. A simple monosaccharide precursor. Lipid X, is shown in Table 3.1. 

Sayers, T., Macher, I., Chung, J., and Kuhler, E. (1987). The production of tumor necrosis factor by mouse bone marrow-derived macrophages in response to bacterial lipopolysaccharide and a chemically-synthesized monosaccharide precursor. J. Immunol. 138,2935-2940. 

The Subcellidar Sites of Monosaccharide Precursor Incorporation into Liver Glycoprotein... 

The incorporation of the monosaccharide precursors discussed in the previous section has been used as a tool to study the subcellular sites of glycoprotein biosynthesis in liver. These experiments will be discussed in this section. 

Ray, B. L., Painter, G., and Raetz, C. R. H. (1984). The biosynthesis of gramnegative endotoxin formation of lipid A disaccharides from monosaccharide precursors in extracts of... 

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