Synthesis of the Lewis b hexasaccharide and squarate acid-HSA conjugates thereof with various saccharide loadings

The Lewis b hexasaccharide, alpha -L-Fucp-(1 --> 2)-beta -D-Galp-(1 --> 3)-[alpha -L-Fucp-(1 --> 4)]-beta -D-GlcpNAc-(1 --> 3)-beta -D-Galp-(1 --> 3)-beta -D- Galp-(1 --> 4)-beta -D-Glcp, has been synthesised using a convergent synthesis. Starting from ethyl 4,6-O-benzylidene-2-deoxy-2-phthalimido-1-thio-beta -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 3(I),4(I)-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. (C) 2000 Elsevier Science Ltd. All rights reserved.