An efficient strategy toward the synthesis of large-ring cyclodextrin (CD) analogs alternating α,αA-trehalose disaccharide subunits and pseudoamide segments (cyclotrehalans, CTs), involving a bimolecular macrocyclization reaction as the key step, is reported. NMR and molecular modeling confirmed that the eight and ten α-D-glucopyranoside subunits in tetrameric and pentameric CT homologues (CT4 and CT5, respectively) are magnetically equivalent, as in the γ and εCD counterparts. Yet, the orientation of the monosaccharide constituents is reversed in CTs as compared with CDs, the β-face being directed to the inside of the nanometric cavity while the α-face remains in contact with the bulk solvent. Molecular mechanics and dynamics experiments revealed that the cyclooligosaccharide architecture in CT4 and CT5 is relatively flexible, which is in contrast to that previously observed for the first members of the CT series (CT2 and CT3 oligomers). Thus, although in their fully expanded conformation their cavity size is close to that of γCD, the higher mobility of the pseudoamide bridges as compared with classical glycosidic linkages endows these hosts with induced fitting capabilities toward smaller guests. © 2009 American Chemical Society.
|Journal||Journal of Organic Chemistry|
|Publication status||Published - 17 Apr 2009|