Synthesis of a αMan(1→3)αMan(1→2)αMan glycocluster presented on a β-cyclodextrin scaffold

Application of 6-thio-alpha- and beta-cyclodextrins as the core component for the construction of multivalent carbohydrate structures is described. The method employed for the attachment of monomeric glycosides to a cyclodextrin core is based on the efficient nucleophilic displacement of bromide from an N-bromoacetamido functionality. The N-bromoacetyl group was positioned at the end of a spacer arm of glycosides and reacted with thiol groups present on the primary face of thiolated cyclodextrins. This coupling reaction led to perfunctionalised cyclodextrins which were thiother-linked to appended saccharides through a short spacer arm. Both components of the key conjugation step - 6-thiocyclodextrins and monomeric glycosides - were used without protecting groups, thus facilitating isolation and purification of target compounds. Glycoclusters incorporating six and seven alpha-D-mannopyranose or beta-D-glucopyranose residues linked to cyclodexrin cores were synthesized in 57-75% yield. Using the same technique, 3-(2-bromoacetamido)propyl trioside, incorporating a synthetic Man-alpha-(1 -> 3)-Man-alpha-(1 -> 2)-Man fragment of antigenic yeast marman, was attached to per-6-thio- beta-cyclodextrin to afford a heptavalent glycocluster. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).