Conformational study on ketamine by circular dichroism and ultraviolet spectroscopy

Since the enantiomers of the N-methyl-D-aspartate (NMDA) receptors antagonist ketamine have different pharmacological profiles, CD and UV spectroscopy were applied for the study of conformer equilibrium and DH dependence in ketamine solutions. The assignment of the configurations and conformations was performed on the basis of the "octant rule" and UV spectra. In accord with published data, it was established that, on protonation, the phenyl group of the ketamine molecule occupies an axial position, while for the base form, the ratio of conformers containing axial/ equatorial aryl moieties is strongly solvent-dependent. The CD and UV spectra indicate the presence of an intramolecular H-bond C=O .... H-N in the conformer with axial aryl moiety. Chirality 11:280-285, 1999. (C) 1999 Wiley-Liss, Inc.