Glycoside-clustering round calixarenes toward the development of multivalent ligands. Synthesis and conformational analysis of Calix[4]arene O- and C-glycoconjugates

Bis- and tetra-O- and C-glycosyl calixarenes (calixsugars) have been prepared by tethering carbohydrate moieties to a tetrapropoxycalix4]arene scaffold through alkyl chains. Two methodologies have been employed. One consisted of the stereoselective multiple glycosylation of upper rim calix4]arene polyols leading to calix-O-glycosides; the other involved a multiple Wittig olefination of upper rim calix4]arene-derived polyaldehydes by the use of sugar phosphoranes and reduction of the alkene double bonds affording calix-C-glycosides. The NMR spectra and NOE experiments of bis-glycosylated products indicate that compounds bearing sugar-protected residues exist preferentially in solution in a flattened cone arrangement (far conformation) whereas deprotected derivatives adopt a close conformation. Calculations by molecular mechanics of the latter compounds point to a close conformation as well in gas phase.