Synthesis of octyl S-glycosides of tri- to pentasaccharide fragments related to the GPI anchor of Trypanosoma brucei

Abstract

The three oligosaccharide octyl-S-glycosides Man-α1,6-Man-α1,4-GlcNH 2-α1, S-Octyl ( 19), Man-α1,6-(Gal-α1,3)Man-α1,4-GlcNH 2-α1, S-Octyl ( 27) and Man-α1,2-Man-α1,6-(Gal-α1,3)Man-α1,4-GlcNH 2-α1, S-Octyl ( 37), related to the GPI anchor of Trypanosoma brucei were prepared by a stepwise and block-wise approach from octyl 2-azido-2-deoxy-3,6-di- O-benzyl-1-thio-α- d-glucopyranoside ( 8) and octyl 2- O-benzoyl-4,6- O-(1,1,3,3-tetraisopropyl-1,3-disiloxane-1,3-diyl)-1-thio-α- d-mannopyransoside ( 9). Glucosamine derivative 8 was obtained from 1,3,4,6-tetra- O-acetyl-2-azido-2-desoxy-β- d-glucopyranose ( 1) in five steps. Mannoside 9 was converted into the corresponding imidate 12 and coupled with 8 to give disaccharide octyl-S-glycoside 13 which was further mannosylated to afford trisaccharide 19 upon deprotection. Likewise, mannoside 9 was galactosylated, converted into the corresponding imidate and coupled with 8 to give trisaccharide 25. Mannosylation of the latter afforded tetrasaccharide 27 upon deprotection. Condensation of 25 with disaccharide imidate 35 gave, upon deprotection of the intermediates, the corresponding pentasaccharide octyl-S-glycoside 37. Saccharides 19, 27 and 37 are suitable substrates for studying the enzymatic glycosylation pattern of the GPI anchor of T. brucei.