Methods for Glycosidic Bond Formation

Inspired by the success of solid-phase peptide and oligonucleotide syntheses, in the early 1970s several research groups attempted to develop methods for solid-supported oligosaccharide synthesis.53 However, since the early methods for glycosidic bond formation were rather restricted, the success of these solid-phase strategies was limited and only simple di-and trisaccharides could be obtained. 

The biological significance of oligosaccharides and glycoconjugates has stimulated many activities in carbohydrate chemistry. Most of these activities have been devoted to the development of methods for glycoside bond formation as the assembly of monosaccharide building... 

Scheme 7. The sulfoxide method for glycoside bond formation (a) and its application (b) to the synthesis of a hexasaccharide p-mannan found in bacterial antigens (35). (Crich, 2001 ) ...

Among all the synthetic methods developed for glycosidic bond formation, the trichloroacetimidate method developed by Richard Schmidt and coworkers [18] is probably the most popular and widely used for the synthesis of complex oligosaccharides. Glycosyl trichloroacetimidates can be readily prepared by a base-catalyzed addition of the anomeric hydroxy group to trichloroacetonitrile. The stereochemistry can be influenced by the addition of different bases the use of K2C03 favors formation... 

These demands were not met by any of the above-described methods for the synthesis of complex oligosaccharides and glycoconjugates. However, the general strategy for glycoside bond formation seems to be correct ... 

W-(phenylthio)caprolactam 19 [66] has been applied as a new promoter for the activation of thioglycosides. Then 19 reacts with trifluoromethansulfonic anhydride, which subsequently activates the thioglycoside for glycosidic bond formation (Scheme 9). Notably, the reaction proceeds efficiently at room temperature and is adaptable to our reactivity-based one-pot oligosaccharide synthesis. This overcomes some limitations of the current methods and, more importantly, proceeds efficiently at room temperature, which is very helpful for the development of one-pot glycosylation machine. 

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