Nuclear magnetic resonance and molecular orbital study of some cocaine analogues

H-1 NMR spectra of (-)-cocaine and some of its derivatives (alpha-CPT, beta -CPT, nor-beta-CIT, cocaine-HCl and ecgonine-HCl) were analysed and the spe ctral parameters were used for conformational analysis of the compounds in conjunction with theoretical HF/6-31G*. MMP2, AMI and molecular dynamics ca lculations. Comparison of the experimental and theoretical data reveals tha t the compounds are predominantly in a rigid chair conformation, which is r ather similar for all compounds. No large differences were found in the dyn amical behaviour of the molecules. The performance of the Haasnoot and Alto na equations is discussed. (C) 1999 Elsevier Science Ltd. All rights reserv ed.