Glycosidic tethering

For conversion of amide to other acid derivatives, a novel synthesis of urea glycosides in aqueous media has been reported via the reaction of Steyermark s glucosyl carbamate with amines in good yields (Eq. 9.17).38 This method was successfully applied to develop a new route to the synthesis of urea-tethered neo-glycoconjugates and pseudooligosaccharides. 

Doi T, Sugiki M, Yamada H, Takahashi T, Porco JA, Jr. Glycosidation of solid-supported glycosyl donors tethered by a trialkylsilane linker. Tetrahedron Lett 1999 40 2141-2144. 

A bacterial phosphatidylinositol specific phospholipase C (PI-PLC) had been available for many years before it was demonstrated to strip a number of membrane-bound proteins from eukaryotic cell surfaces [1], Such proteins are anchored by a PI moiety in which the 6 position of inositol is glycosidically linked to glucosamine, which in turn is bonded to a polymannan backbone (Fig. 3-10). The polysaccharide chain is joined to the carboxyl terminal of the anchored protein via amide linkage to ethanolamine phosphate. The presence of a free NH2 group in the glucosamine residue makes the structure labile to nitrous acid. Bacterial PI-PLC hydrolyzes the bond between DAG and phosphati-dylinositols, releasing the water-soluble protein polysac charide-inositol phosphate moiety. These proteins are tethered by glycosylphosphatidylinositol (GPI) anchors. 

Ziegler and coworkers prearranged a glycoside by employing a succinyl tether between C-6 of a mannosyl donor and C-3 of glucosyl acceptor [151,152]. They found that the nature of the glycosyl acceptor and the length of the tether affected the anomeric selectivity of the intramolecular mannosylation (Scheme 4.4d) [153]. 

The IAD concept via p-methoxybenzylidene acetals was also shown to be suitable for polymer-supported syntheses of disaccharides (Scheme 5.107) [292], A suitable p-allyloxybenzyl group at position 2 of a 1-thio-mannosyl donor is first converted into a PEG-modified benzyl group that allows for the convenient isolation of the intermediate tethered glycosides. 

IAD via Silylene Tethering IAD through silylene-tethered glycosides was introduced by Bols [296-301] and Stork [302,303], The silylene tether is usually established by... 

Yet another approach uses peptides as tethers for intramolecular glycosylations via prearranged glycosides (Scheme 5.113) [326,327]. The regio- and anomeric selectivity of the intramolecular glycosylation depends on the amino acid sequence of the peptide, which links glycosyl donor and acceptor. 

The base lability of succinoyl diester hnker severely limits the selection of protecting groups available for an oligosaccharide synthesis, so a more versatile tether was required. Diether bonds of benzylphenol or dibenzyl of 1,4-di(hydroxymethyl)-benzene satisfy this requirement because they are stable to both bases and to acids. A sufficient acid stability is important since the formation of a glycosidic bond is an acid-catalyzed reaction, not surprisingly, as it is an acetal functionality. For instance, DOX,34 the dibenzyl hnker a,a -DiOxyXylyl diether, -0CH2C6H4CH20-, is not limited by restriction of the succinoyl hnker (1) when bound via a hydroxyl or as an... 

C-Glycoside synthesis may be achieved in twro ways. Intermolecular radical addition reactions are observed with (i) polarized, electron-deficient alkenes, (ii) alkenes that provide a high level of stabilization to the initial radical adduct and (in) substrates that undergo a facile fragmentation (e.g. allyl stannanes). Additions to less reactive substrates, though not favored for intermolecular processes, are observed if the two components are tethered in an intramolecular array. 

Glycosides of the disaccharide p-Tyv-(l- 3)-p-D-GalNAc (139)221 and the trisaccharide epitope 140 carrying the challenging (3-1,2-cis-linked tyvelose of the Trichinella antigen were synthesized. The co-amino tether 141 and the fluorescein conjugate 142 of the trisaccharide were described.222... 

An acetal tethered compound can easily be prepared by treatment of equimolar amounts of a 2-propenyl ether derivative of a saccharide with a sugar hydroxyl in the presence of a catalytic amount of acid. Activation of the anomeric thio moiety of the tethered compound with N-iodosuccinimide (NIS) in dichloromethane results in the formation of the p-linked disaccharide. In this reaction, no a-linked disaccharide is usually detected. It is of interest to note that when this reaction was performed in the presence of methanol, no methyl glycosides are obtained. This experiment indicates that the glycosylation proceeds via a concerted reaction and not a free anomeric oxocarbenium ion. 

Regioselective synthesis of unsymmetrical C-aryl glycosides using silicon tethers, as disposable linkers, has been developed (Scheme 55). Deprotonation of 304 with Bu Li led to the formation of an intermediate benzyne 305 that underwent cycloaddition to deliver 306. When 306 was treated with TBAF in DMF at 70°C, the tether was cleaved and 307 was obtained in 80% yield. The acid-catalyzed opening of the oxabicycloheptadiene ring afforded the glycosyl naphthols 308 in quantitative yield <2003JA12994>. 

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