Synthesis of 3-O-sulfoglucuronyl lacto-N-neotetraose 2-aminoethyl glycoside and biotinylated neoglycoconjugates thereof

The 2-aminoethyl glycoside of pentasaccharide 3-O-sulfo-GlcA(beta -1 --> 3) Gal(beta -1 --> 4)GlcNAc(beta -1 --> 3)Gal(beta -1 --> 4)Glc(beta (1) and i ts conjugates with biotin and biotinylated polyacrylic acid were synthesize d as molecular probes to investigate the recognition of the HNK-1 epitope c ontaining carbohydrates by proteins. Key steps in the first of two investig ated schemes for the preparation of the target compound 1 were (a) assembli ng of the pentasaccharide backbone (compound 10) by glycosylation of select ively substituted allyl glycoside of the trisaccharide GlcNAc(beta -1 --> 3 )Gal(beta -1 --> 4)Glc(beta with glucuronyl-galactose glycosyl donor, (b) t ransformation of the allyl aglycon in 10 into 2-azidoethyl one (to give 11) , (c) selective deprotection of the OH group at C-3 of the GlcA residue in 11 via saponification, intramolecular formation of 6,3-lacton (13) and its methanolysis, and (d) subsequent O-sulfation. The alternative scheme with t he use of 2-azido-ethyl glycoside of the trisaccharide GlcNAc(beta -1 --> 3 )Gal(beta -1 --> 4)Glc(beta instead of the allyl glycoside 6 was less effec tive due to smaller yield at the step of pentasaccharide synthesis. Additio nally to 1 the 2-aminoethyl glycosides of the oligosaccharides GlcA(beta -1 --> 3)Gal(beta -1 --> 4)GlcNAc(beta -1 --> 3)Gal(beta -1 --> 4)Glc(beta, 3 -O-sulfo-GlcA(beta -1 --> 3)Gal(beta, and GlcA(beta -1 --> 3)Gal(beta were also synthesized. (C) 2000 Elsevier Science Ltd. All rights reserved.