Synthesis, Structure, and Inclusion Capabilities of Trehalose-Based Cyclodextrin Analogues (Cyclotrehalans)

Concise and efficient strategies toward the synthesis of D2h- and D3h-symmetric cyclodextrin analogues
alternating α,α‘-trehalose disaccharide subunits and pseudoamide segments (cyclotrehalans, CTs) are
reported. The conformational properties of these cyclooligosaccharides are governed by the rigidity of
the α,α‘-trehalose disaccharide repeating unit and the partial double-bond character of the N−(CX)
linkages. In contrast to the typical concave-shaped cavity of cyclodextrins (CDs), CTs feature a convex-shaped hydrophobic cavity in which the β-face of the monosaccharide subunits is oriented toward the
inner side, as supported by NMR and modeling (molecular mechanics and dynamics) studies. In the case
of cyclodimeric CTs (CT2s), the existence of intramolecular hydrogen bonds results in collapsed cavities,
too small to allow the formation of inclusion complexes with organic molecules. Cyclotrimeric CTs
(CT3s) display cavity sizes that are intermediate between those of αCD and βCD, ideally suited for the
complexation of complementary guests with ternary symmetry such as adamantane 1-carboxylate (AC).
The higher flexibility of the pseudoamide bridges as compared with classical glycosidic linkages endow
these glyconanocavities with some conformational adaptability properties, making them better suited
than CDs for complexation of angular guests, as seen from comparative inclusion capability experiments
against the fluorescent probes 6-p-toluidinonaphthalene-2-sulfonate (TNS; linear) and 8-anilinonaphthalene-1-sulfonate (ANS; angular).