Chiral discrimination of the analgesic cizolirtine by using cyclodextrins: A 1H NMR study on the solution structures of their host–guest complexes

Abstract

The use of four cyclodextrins (three native and one ␤-CD derivative) as NMR chiral solvating agents to resolve the enantiomers of (±)-cizolirtine, 1, and its chemical precursor (the carbinol, (±)-2), was investigated. The best enantiodiscrimination occurred when ␤-cyclodextrin was used. ROESY experiments were performed to qualitatively ascertain the most probable host-guest structures in D 2 O solution, and the binding features found were explained in terms of spatial fitting of the guest molecules into the macrocyclic cavities. No geometrical differences were noted between the two diastereomeric complexes formed by a cyclodextrin and a racemic substrate, so the magnetic nonequivalence induced on guest protons by the enantioselective binding had to be explained as a result of subtle disparities in the orientation and/or the conformational state of the complexed enantiomers.

Multicomponent complex formation between vinpocetine, cyclodextrins, tartaric acid and water-soluble polymers monitored by NMR and solubility studies

“…In what concerns guest resonances, although there is a general tendency for chemical shift displacements, upfield for the aromatic protons and downfield for the other ones, there is no simple explanation in terms of inclusion or non-inclusion. The chemical shift displacement of VP protons must be regarded as a result of a combination of interactions with the macrocycle and time-averaged conformational changes of the included molecules (Redondo et al, 1999). Nevertheless, the downfield shift of the resonances of the alkyl protons was ascribed to the interaction with the hydrophilic external part of the CD molecule (Uccello-Barretta et al, 1993) and to conformational changes produced by the inclusion (Redenti et al, 1999).…”

Molecular Modeling of the Chiral Recognition of Propranolol Enantiomers by a β-Cyclodextrin

“…6 β-Cyclodextrin (β-CD) is a macrocyclic molecule formed by α-(1 → 4) glycosidic links between seven D-glucose monomer units, adopt a toroid shape. The resulting cavity of the cyclodextrins well characterized complexing properties with the appropriate guest molecules.…”