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

The use of four cyclodextrins (three native and one beta-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 beta-cyclodextrin was used. RO ESY experiments were performed to qualitatively ascertain the most probable host-guest structures in D2O solution, and the binding features found were explained in terms of spatial fitting of the guest molecules into the macr ocyclic cavities. No geometrical differences were noted between the two dia stereomeric complexes formed by a cyclodextrin and a racemic substrate, so the magnetic nonequivalence induced on guest protons by the enantioselectiv e binding had to be explained as a result of subtle disparities in the orie ntation and/or the conformational state of the complexed enantiomers. (C) 1 999 Wiley-Liss, Inc.