chapter 2 - Bentham Science

Cyclopeptide-Based Glycoclusters Synthesis and Biological Applications of Glycoconjugates 131
Figure 2: Synthesis of sialyl-Le x containing cycloheptapeptide conjugates.
Plant Lectins
To overcome the synthetic difficulties related to the synthesis of glycoconjugates, our group developed an oximebased
chemoselective procedure that revealed extremely efficient for the construction of CBGs [39]. This strategy
requires the prior incorporation of mutually reactive aldehyde and oxyamine groups into the molecules to be
conjugated. Only few procedures (i.e. Mitsunobu coupling [40], stereoselective glycosylation using phase transfer
catalysis [41]) were reported to introduce an aminooxy function to the anomeric position of glycans. We developed
a synthetic alternative to afford alpha and beta aminooxy glycosyls starting from glycosyl fluoride donors and Nhydroxyphthalimide
(PhthOH) in the presence of BF3.Et2O as promoter [42] (Fig. 3). This strategy was used
successfully to synthesize biologically relevant carbohydrates (e.g. lactose 4, mannose 7 and fucose 8 [43]) or
tumor-associated carbohydrate antigens (e.g. Tn 9 and Thomsen-Friedenreich (TF) 10 [44]).
Figure 3: Synthesis of aminooxy glycosyls.
With these aminooxy glycosyls in hands, glycoclusters with one or two addressable domains were next designed.
Typically, linear peptides containing a various number of orthogonally protected Lys (e.g. Alloc, Boc, Dde) were
prepared on solid-phase using acido labile resin (e.g. Sasrin TM ) then cyclised in solution through the C-terminal
glycine to prevent epimerization. To design one domain-containing compounds, four Lys pointing above the
platform were deprotected to incorporate serine residues. Successive treatment with sodium periodate generate
glycoxyl aldehyde groups [45]. Fully deprotected aminooxy glycosyls were finally conjugated under mild aqueous