Synthesis of a D,D- and L,D-heptose-containing hexasaccharide corresponding to a structure from Haemophilus ducreyi lipopolysaccharides

The synthesis of a linear hexasaccharide, 2-(4-trifluoroacetamidophenyl)eth yl (beta-D-galactopyranosyl)-( 1--4)-(2-acetamido-2-deoxy-beta-D-glucopyran osyl)-(1 --> 3)-(beta-D-galactopyranosy1)-(1-->4)-(D-glycero-alpha-D-manno- heptopyranosyl)-(1-->6)-(beta-D-glucopyranosyl)-(1-->4)-L-glycero-alpha-D-m anno-heptopyranoside, corresponding to a structure found in Haemophilus duc reyi LPS, is described. A Barbier reaction between benzyloxymethyl chloride and a properly protected 6-aldo-1-thio-mannopyranoside yielded both the D, D- and the L,D-heptopyranoside (2 and 3, ratio 2:3), which were separated a nd both used in the synthesis, p-Methoxybenzyl and chloroacetyl groups were employed as temporary protecting groups, selectively removed in the presen ce of the persistent benzyl, acetyl, benzoyl and isopropylidene groups by t reatment with DDQ/H2O and hydrazine dithiocarbonate, respectively. Thioglyc osides were utilised as donors throughout using either NIS/TfOH or DMTST as promoters. The introduction of the spacer into thioglycoside 5 was high-yi elding (95%) but with low stereoselectivity (alpha:beta 5:3). All other gly cosylations are completely stereoselective. The target hexasaccharide is ob tained via a 3+3 block approach with the yield in the final NIS/TfOH-promot ed coupling between an N,N-diacetyl-trisaccharide thioglycosyl donor 20 and a 4 "-OH trisaccharide acceptor 13 being 75%. (C) 2000 Elsevier Science Lt d. All rights reserved.