Stereoselectivity, of glycosylation reactions

This synthesis demonstrated that the neighboring-group participation effect on the stereoselectivity of glycosylation reactions can be extended to sohd-phase processes. In this case, milder and more practical cleavage conditions than previously discussed were established. The use of /V- bromosuccinimide as the thiophilic reagent in acetone/water or tetrahydrofuran/methanol permitted the release of oligosaccharides in form of lactols or 1-0-Me glycosides, respectively. The tetrasaccharide derivative was isolated in 34% yield from thiol resin 3 (80% yield per step). 

Other common approaches to control the stereoselectivity of glycosylation will be discussed in the subsequent sections. In addition to the apparent complexity of the glycosidation process, there are other competing processes that cannot be disregarded. These reactions often cause the compromised yields of the glycosylation products and further complicate the studies of the reaction mechanism. 

The reaction conditions also significantly influence the stereoselectivity of glycosylations. Solvents are particularly important in this respect. To achieve stereoselectivity, reactions should... 

A different approach to control the stereoselectivity of glycosylations is through the use of heterogeneous catalysis. Catalysts such as silver silicate were developed for this purpose [46]. Reactions of glycosyl halides on the surface of silver silicate are thought to proceed by a concerted mechanism providing, for example, (3-D-mannopyranosides 44 from a-D-mannosyl bromide 43 (Scheme 4.7). 

SCHEME 4.6 The effect of the promoter and the reaction conditions on the stereoselectivity of glycosylations. 

As shown, the glycosylation reaction of the succinoyl tethered compounds (157, 159 and 161) was performed by promotion with NIS and TMSOTf in acetonitrile. The (2 -3)-tethered compound (157) afforded the a-glucopyranoside (158) in excellent yield. Similarly, the (2 -3)-tethered (159) and also the (6 -3)-tethered (161) galactose derivatives afforded the cis-glycosides (160 and 162). The stereoselectivity of these reactions is noteworthy as both the acyl-type neighboring group in the donor and the nitrile type solvent favor trawi-glycoside formation. 

C. G. Lucero and K. A. Woerpel, Stereoselective C-glycosylation reactions of pyranoses The conformational preference and reactions of mannosyl cation, J. Org. Chem., 71 (2006) 2641-2647. 

Indeed, the stereoselectivity in glycosylation reactions with glucosyl fluoride was strongly affected by the anion moiety of the ionic liquid employed, as shown in Table 3.2. 

Larsen CH, Ridgway BH, Shaw JT, Smith DM, Woerpel KA (2005) Stereoselective C-glycosylation reactions of ribose derivatives electronic effects of five-membered ring oxocarbenium ions. J Am Chem Soc 127 10879-10884... 

Aldiough it is clear diat a modification at die S-N position of N-acetylneuraminic acid influences reactivity and stereoselectivity in glycosylation reactions, a universal S-N protecting group that would address all the challenges of sialylation has not yet emerged. 

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