Synthesis of phosphorylated Neisseria meningitidis inner core lipopolysaccharide structures

A phosphoethanolamine-substituted tetrasaccharide structure, 2-aminoethyl 2-acetamido-2-deoxy-alpha-D-glucopyranosyl-(1 -> 2)-6-O-[2-(tert-butyloxycarbonylaminoethyl)-phophono]-L-glycero-alpha-D-manno-heptopyranosyl-(1 -> 3)-[beta-D-glucopyranosyl-(1 -> 4)]-L-glycero-alpha-D-manno-heptopyranoside,corresponding to the non-reducing part of the conserved part of Neisseria meningitidis lipopolysaccharides has been synthesized. Orthogonal protection of the phosphoethanolamino group in combination with the presence of a free amino-containing anomeric spacer allows conjugation to proteins to construct conjugate vaccine candidates. The tetrasaccharide is built up using a linear strategy, where the introduction Of the terminal alpha-GlcNAc moiety is performed using a 2-azido-thioglucoside as a donor and NIS/AgOTf as a promoter. The synthetic pathway includes tetrasaccharide intermediates appropriately designed to permit other phosphorylation patterns as well as elongation at the reducing end. (C) 2009 Elsevier Ltd. All rights reserved.