SYNTHESIS OF SIALYL-alpha-(2->3)-NEOLACTOTETRAOSE DERIVATIVES MODIFIED AT C-2 OF THE N-ACETYLGLUCOSAMINE RESIDUE: PROBES FOR INVESTIGATION OF ACCEPTOR SPECIFICITY OF HUMAN alpha-1,3-FUCOSYLTRANSFERASES, FUC-TVII AND FUC-TVI

摘要

A variety of siaryl-alpha-(2->3)-neolactotetraose (IV~3NeuAcnLc0se_4 or IV~3NeuGcnLc0se_4) derivatives (23, 31-37, 58-60) modified at C-2 of the GlcNAc residue have been synthesized. The phthalimido group at C-2 of GlcNAc in 2-(trimethylsilyl)ethyl (3,6-di-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-(l->3)-(2,4,6-tri-O-benzyl-(3-D-galactopyranosyl)-(1->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside (5) was systematically converted to a series of acylamino groups, to give the per-O-benzylated tri-saccharide acceptors (6-11). On the other hand, modification of the hydroxyl group at C-2 of the terminal Glc residue in 2-(trimethylsilyl)ethyl (4,6-0-benzylidene-P-D-glucopyranosyl)-(l->3)-(2,4,6-tri-O-benzyl-beta-D-galactopyr-anosyl)-(l->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside (42) gave three different kinds of trisaccharide acceptors containing D-glucose (49), N-acetyl-D-mannosamine (50), and D-mannose (51) instead of the GlcNAc residue. Totally ten trisaccharide acceptors (5-11 and 49-51) were each coupled with sialyl-alpha-(2->3)-galactose donor 12 to afford the corresponding pentasacchar-ides (14-21 and 52-54) in good yields, respectively, which were then transformed into the target compounds. Acceptor specificity of the synthetic sialyl-alpha-(2->3)-neolactotetraose probes for the human alpha-(l->3)-fucosyltrans-ferases, Fuc-TVII and Fuc-TVI, was examined.