Synthesis of a tetrasaccharide using

Scheme 2.6 Solid-phase synthesis of a tetrasaccharide using the glycal assembly method.

Scheme 4. Synthesis of a tetrasaccharide using a variety of reaction conditions.

Applications Using these protocols, an oligosaccharide library was prepared (Table 11.2). The synthesis of a tetrasaccharide in general, takes 3-15 min, and with the aid of the computer program, a library of individual oligosaccharides can be assembled rapidly. 

The coupling protocols described in the two previous examples can be combined to allow for the synthesis of branched carbohydrates.19 The automated solid-phase synthesis of a tetrasaccharide is illustrated in Scheme 4. Both glycosyl phosphate and glycosyl imidate building blocks were used along with acetate and levulinate esters as temporary protecting groups. 

Some disappointing results were reported later by the same group in an attempt to use phenyl selenoglycoside donors for the synthesis of a tetrasaccharide.86 No glycosylation was possible with phenyl selenoglycoside 193 in the presence of NIS-TfOH, whereas 40% yield was obtained with the corresponding trichloroacetimidate 194. 

This procedure was also employed using glycosyl fluorides as donors [84] and was applied for the synthesis of a-D-glucopyranosides [83,84]. However, only a modest yield was obtained when it was applied to the synthesis of a tetrasaccharide [85]. 

Scheme 8.1 Synthesis of a sialyl-Lewis tetrasaccharide employing C-enriched protecting groups for the quantitative reaction monitoring using gated decoupling NMR spectroscopy.

The validity of the approach was first demonstrated by the synthesis of a linear tetrasaccharide [22] and a hexasaccharide 13 [23] as outlined in Scheme 3. Polymer-bound galactal 5 was converted to the 1,2-anhydro sugar 6 by epoxidation with 3,3-dimethyldioxirane [24], Polymer-bound 6 acted as a glycosyl donor when reacted with a solution of 7 in the presence of zinc chloride, resulting in the formation of disaccharide 8a. Upon repetition, this glycosylation procedure accommodated the secondary alcohol glycosyl acceptor 10 as well as disaccharide acceptor 12. Huor-idolysis with tetrabutylammonium fluoride (TBAF) was used to cleave the desired products from the polymeric support and furnish hexasaccharide 13 in 29% overall yield from 5 [16]. 

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