C-Mannosides

Using this methodology, a-C-dissacharides [21] and oc-C-mannosides such 14 are synthesized by radical intermediates which can adopt chair conformations (Scheme 7). 

Examination of specific carbohydrate-protein interactions can be accomplished with C-glycosides (Scheme 1). A series of C-glucosides and C-mannosides, such as 1, were employed to study the binding differences between mannose and glucose specific lectins (9). C-Mannoside derivatives (3-5) were synthesized from C-allyl derivative 2 and used to block cell-surface lectins thereby inhibiting bacterial adhesion (JO). The primary amine of 4 was functionalized with biotin to target proteins to the bacterial cell surface. 

The aromatic phenol was varied to explore the scope of the O-to-C conversion with mannosyl phosphates. Using phosphate 9, the a-C-mannosides of 2-naphthol and 3-benzyloxy phenol (23 and 25, Table 1) were synthesized in excellent yield. O-Mannosides were obtained exclusively with less nucleophilic aromatic systems, such as 3-acetoxy phenol. Several non-phenolic aromatic systems were unsuccessful in the formation of C-aryl or O-aryl glycosides. Reaction of 9 with furan, thiophene, trimethoxybenzene, and indole in the presence of TMSOTf did not result in any product formation. Interestingly, activation of 9 in the absence of any aromatic nucleophiles gave 26 as the major product via an intramolecular C-glycosylation (Figure 1) (79). 

Pathogenic organisms are known to use carbohydrate receptors such as lectins to bind to cell surfaces.77 70 Type I pili, a type of proteinaceous appendage, are found on the surface of Escherichia coli30 and contain receptors capable of binding to a-linked mannosides.8183 In 1992, Bertozzi, ef a/.,84 Prepared new C-mannosides that bind to Escherichia coli receptors and are able... 

The same group used a ketal tether as an alternative connecting group in the synthesis of the 1,4-linked C-disaccharide 236 [85 b]. Tebbe methylenation of acetate 237 provided the corresponding enol ether 238, which upon treatment with alcohol 235 in the presence of CSA at -40°C in acetonitrile, furnished linked disaccharide 239 in 81% yield. Subsequent radical cyclization, acidic hydrolysis of the tether and peracetylation provided the D-mannose-containing C-disaccharide 236 as the major product in 35% yield from 239 (Scheme 10-75). Cyclization was not completely stereoselective and a small amount of the )8-C-manno isomer was also isolated (a/)3 10 1). This result is in contrast to similar studies on tether-directed /J-C-mannoside syntheses (vide infra) where a much shorter tether attached to the axial 2-hydroxyl group forces obtention of the desired P-configuration. 

The previous examples demonstrate that intermolecular mannosylations proceed with high p-selectivity only with donors that are structurally disposed to direct Sn2-type substitution at the anomeric carbon and disfavor the formation of oxocarbonium ion intermediates. Because of the large number of variables, the steric outcome of intermolecular mannosylations is predictable only in closely related systems. Stork has proposed a conceptually new, intramolecular mannosylation protocol that has initially been implemented in the first stereocontrolled synthesis of a p-C-mannoside [108]. The starting compound is the phenylseleno mannoside 34 in which a 2-phenylethynyl group is anchored to 0-2 through a silicon tether. Radical-initiated removal of the anomeric phenylseleno group (— 35) in concert with cycliza-tion of the phenylethynyl group on to the anomeric radical provides 36 from which fluoride-mediated detachment of the silicon connector affords p-C-mannoside 37 (Scheme 12). 

DAHP, 64) [135], an intermediate of the shikimic acid pathway, have been synthesized from corresponding aldehyde precursors. Several cychtols (e.g., 71-73) could be made from aldol products by radical or nucleophilic cyclization reactions [136-138]. An intermediate was also found to be a correctly configurated precursor to the spirocyclic Strep-tomyces metabolite sphydrofuran 69 [139]. In an approach resembling the inversion strategy an a-C-mannoside 68 has been prepared from D-ribose 5-phosphate [140]. 

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