SYNTHESIS OF SIALYL LE(X) GANGLIOSIDE ANALOGS MODIFIED AT C-6 OF THE GALACTOSE RESIDUE TO ELUCIDATE THE MECHANISM OF SELECTION RECOGNITION

Sialyl Lewis X ganglioside analogues modified at C-tl of the galactose residue, having 6-O-methoxy, 6-acetamido and 6-amino functional group s, have been synthesized. Treatment of 2-(trimethylsilyl)ethyl (methyl nate)-(2-->3)-2-O-benzoyl-beta-D-galactopyranoside with trimethyloxon ium tetrafluoroborate or Tf2O, followed by NaN3, gave the 6-O-methyl a nd 6-azido derivatives, respectively, which were converted into their respective methyl 1-thioglycoside derivatives. The glycosyl donors obt ained were coupled with 2-(trimethylsilyl)ethyl 1-->4)-2,3,6-tri-O-ben zyl-beta-D-galactopyranoside in the presence of dimethyl(methylthio)su lfonium triflate (DMTST) to give their respective pentasaccharides. Th e glycosylation of the pentasaccharide accepters derived from their pr ecursors by removal of the 4-methoxybenzyl group, with phenyl 1-thiogl ycoside derivative of L-fucose using N-iodosuccinimide-TfOH afforded t he corresponding hexasaccharides, which were transformed in good yield , via reductive removal of the benzyl group, the simultaneous transfor mation of azide to amine and acetamide, O-deacylation and saponificati on of the methyl ester into the target compounds without the ceramide groups. On the other hand, the proper manipulation of the protecting g roup of the hexasaccharides, including a transformation of azide into acetamide and trifluoroacetamide, gave the hexasaccharide imidates, wh ich were coupled with -3-O-tert-butyldiphenylsilyl-4-otadecene-1,3-dio l. Selective reduction of the azido group, N-acylation with octadecano ic acid, and the complete removal of the protecting groups gave the de sired sialyl Le(X) ganglioside analogues. (C) 1998 Elsevier Science Lt d. All rights reserved.