Synthesis of the Lewis b hexasaccharide and squarate acid–HSA conjugates thereof with various saccharide loadings Original Research Article

The Lewis b hexasaccharide, α-l-Fucp-(1→2)-β-d-Galp-(1→3)-[α-l-Fucp-(1→4)]-β-d-GlcpNAc-(1→3)-β-d-Galp-(1→4)-β-d-Glcp, has been synthesised using a convergent synthesis. Starting from ethyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-1-thio-β-d-glucopyranoside, a thioglycoside tetrasaccharide donor block, was constructed through two orthogonal glycosylations with glycosyl bromide donors. First, the galactose moiety was introduced using silver triflate as a promoter and then the two fucose residues under halide-assisted conditions. Finally, this tetrasaccharide was linked to a spacer-equipped 3I,4I-diol lactose acceptor in a DMTST-promoted coupling to give, after deprotection, the Lewis b hexasaccharide as its 2-aminoethyl spacer-equipped derivative. This was coupled to human serum albumin (HSA), using the squarate ester methodology, in various saccharide–protein ratios, to give neoglycoconjugates with different saccharide loadings in about 50% efficiency.