Synthesis of a αMan(1→3)αMan(1→2)αMan Glycocluster Presented on aβ‐Cyclodextrin Scaffold

Abstract

AbstractApplication of 6‐thio‐α‐ and β‐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 α‐D‐mannopyranose or β‐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‐α‐(1→3)‐Man‐α‐(1→2)‐Man fragment of antigenic yeast mannan, was attached to per‐6‐thio‐β‐cyclodextrin to afford a heptavalent glycocluster. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)