Tethering to the Glycosyl Donor

The acetate was converted to methylene derivative 2 with the Tebbe reagent. Treatment of 2 with the alcohols a, b or c in the presence of a catalytic amount of acid formed the key acetals 3a-3c in moderate yield. Activation of 3a-3c with 5 equiv. A-iodosuccinimide (NIS) resulted in selective intramolecular glycosidation at the P face via intermediates 4a-4c, which on aqueous work-up gave the desired P-mannopyranosides 5a-5c. 

In a later paper an improved method, in which the base 2,6-di-/-butyl-4-methylpyridine (DBMP) was added in the activation step, was reported [5]. This increased the yields of 5b and 5c significantly. Further investigation, by means of competition experiments, showed that the reaction was intramolecular, but also revealed some limitations of the method. The mixed acetals 3a-3d were relatively unstable and had to be prepared carefully to avoid hydrolysis to the corresponding monosaccharides or dimerization. Furthermore the yield dropped drastically when trisaccharides, e.g. 5d, or tetrasaccharides were synthesized [6]. 

R nw Mixed P-glycosideS 9ceiais without base with base  

The basic idea was to trap intermediate 7 under anhydrous conditions and react it with another alcohol producing the corresponding mixed acetal. 

By use of this strategy the core penta- and hexasaccharides found in asparagine-linked oligosaccharides were synthesized in good yield [10-12]. 

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