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

Abstract

Application 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)

Selectivity among Two Lectins: Probing the Effect of Topology, Multivalency and Flexibility of “Clicked” Multivalent Glycoclusters

“…[47] Calix [6]arenes provide interesting scaffolds in which the carbohydrate epitopes will be condensed in a narrow space (although the conformational rigidity of calix [6]arenes is much weaker than for calix [4]arenes) and will create a high-density volume of ligands available for binding to a lectin. To exploit the particularly dense functionalisation of these scaffolds, we have prepared two calix [6]arenes with either three of six propargyl residues and their subsequent condensation with the azido-functionalised carbohydrate probe was achieved by "click" chemistry.…”

“…[2][3][4] The design of multivalent glycoconjugates, [5] such as glycoclusters, [6][7][8][9][10][11] glycodendrimers, [12][13][14] glycopolymers, [15][16][17] and glyconanoparticles [18][19][20][21][22] has brought a large set of data on the binding properties of each class of conjugates with lectins. While the positive influence of multivalency on the affinity to lectins has been clearly demonstrated, the influence of the glycoconjugates topology on the affinity has been scarcely investigated.…”

Cyclodextrin-based multivalent glycodisplays: covalent and supramolecular conjugates to assess carbohydrate–protein interactions

“…86 Carpenter and Nepogodiev employed per-6-thio cyclodextrins as sulfur multinucleophiles and halogen-armed carbohydrates as substrates for the preparation of primary face-anchored glycoclusters, thereby reversing the location of the functional groups involved in the key multiple S N 2 reaction. 89 Per-6-thioaCD and -bCD (19) were obtained from the corresponding per-(C-6)-Br and per-(C-6)-I derivatives, respectively, by reaction with thiourea in the absence of oxygen followed by decomposition of the resulting thiouronium salts with aqueous NaOH. 90 Scheme 8 Synthesis of heptavalent bCD-centred glycoclusters from per-(C-6)-halo derivatives by S N 2 reaction with fully unprotected sugar thiolates.…”

“…The procedure was next extended to the preparation of an heptavalent conjugate 21 incorporating the aMan-(1-3)aMan-(1-2)aMan mannotrioside (20) as a mimic of the outer chains of the mannoproteins of yeast (Saccharomyces cerevisiae), responsible for their allergenicity and antigenicity (Scheme 11). 89 In the search of a high yielding and flexible synthetic strategy to access multivalent CD-based glycoclusters, Fulton and Stoddart investigated the photochemical addition of thiols to allylated-bCD derivatives. Starting from heptakis(6-O-allyl-2,3-di-O-methyl)bCD and per-O-acetylated 1-thiosugars (from bGlc and bLac) the corresponding heptavalent conjugates were obtained in 67 and 69% yield, respectively (Scheme 12).…”

Synthesis of cyclodextrin derivatives with monosaccharides and their binding with ampicillin and selected lectins

“…1 Cyclodextrins (CDs) offer unique features towards the formation of glycoclusters for biological applications, since they are biocompatible and can be easily modified in their primary side with carbohydrate moieties. Per-carbohydrate modified CD derivatives have been reported [6][7][8][9][10][11][12][13][14][15] demonstrating the advantages of multivalency and clustering effect in homo-and heterogeneously decorated cyclodextrin scaffolds. Herein, the synthesis of a series of new cyclodextrin-based glycoclusters with seven and eight monosaccharide units connected to the CD core via optimally sized linkers, as well as the corresponding monosubstituted derivatives, is reported.…”