Macrocyclic Sugar Thioureas: Cyclooligosaccharides Mimicking Cyclopeptides

Abstract

Interactions between carbohydrates and other organic molecules, specially proteins, play a prominent role in many biological recognition processes. The complexity of such phenomena has stimulated the use of model systems to get information about their nature (lipophilic, polar, hydrogen bonds, etc.) and to evaluate their contribution to the stability and specificity of the carbohydrate-containing supramolecular entity. Among model sugar-derived hosts, the natural cyclodextrins (CDs) have been by far the most widely used for this purpose, due to their commercial availability and to the presence of a hydrophobic cavity that can accommodate a guest molecule surrounded by a hydrophilic environment.¹ Contributory reasons to the popularity of CDs are the high symmetry and rigidity of the structure that facilitate the study of inclusion complexes by NMR techniques. However, this lack of conformational flexibility is a limitation regarding efficiency of complexation, since the host cannot adapt its geometry to the guest for an optimal interaction. Such ability is, in contrast, a main structural feature of polyamide receptors, from which cyclopeptides are paradigmatic examples. We have now imported this faculty into cyclic oligosaccharides by inserting thiourea spacers that would act as symmetric amide surrogates. The possibility of switching between Z and E configurations at the pseudoamide linkages allows then a restricted number of rotameric forms whose relative populations are conditioned by the strong hydrogen bond donnor character of the NH thiourea protons.²,³ In addition, these sugar-thiourea coronands may be considered as comformationally restricted glycopeptide analogues, useful as model compounds for the study of specific carbohydrate-peptide interactions, e.g. interactions involving the pseudoamide NH protons and the carbohydrate oxygen atoms.