Glycosylation disaccharide formation

Glycosylation by trityl sugars. Disaccharide formation catalyzed by AgC104-SnCl4 makes it possible to use the more stable trityl sugars (in situ detritylation) as nucleophiles. 

These reactions can be rationalized by envisaging a glycosyl cation intermediate that is subject to competitive interception either by the hydroxyl group of another sugar, leading to disaccharide formation, or by water, leading to overall hydrolysis (Figure 5.2). 

Scheme 10.6 (a) Disaccharide formation by glycosylation reaction of protected mannoside (glycosyl donor) and galactoside (acceptor), (b) Glycosylation reaction involving mannosyl donor and acceptor to form dissacharide. Orthoester was also formed. 

A typical procedure calls for reaction of the hemiacetal donor with dicydohexyl carbodiimide and copper(I) chloride (0.1 equiv) at 80 °C, followed by an addition of the acceptor and continued heating. As an early demonstration of this protocol, oc-riboside 86 was prepared in moderate yield but with exclusive stereoselectivity [141]. Further measures were required for the glycosylation of monosaccharide acceptors, such as addition of p-toluenesulfonic add (0.1 equiv) to promote the formation of disaccharide 87 [144]. The method was more suitably applied to the synthesis of O-acyl glycopeptides, as evidenced by the formation of 88 in 60% yield [143,144]. Various peptides with non-nudeophilic side chains were found to be amenable to this stereoselective reaction. The [3-selectivity was suggested to arise from a preponderance of the a-isourea intermediate 85 in the activation step. 

Although the coupling of glycosyl dithiophosphates using an excess methyl triflate as an activator in the presence of 2,6-di-tertbutylpyridine proceeded in a satisfactory yield (70%), the application of dimethylsulfonium triflate resulted in the formation of disaccharides in a considerably more effective way (94% yield). 

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