CHIRAL DISCRIMINATION BY NMR-SPECTROSCOPY OF EPHEDRINE AND N-METHYLEPHEDRINE INDUCED BY BETA-CYCLODEXTRIN, HEPTAKIS(2,3-DI-O-ACETYL)BETA-CYCLODEXTRIN, AND HEPTAKIS(6-O-ACETYL)BETA-CYCLODEXTRIN

NMR spectroscopy has been used to compare the interaction of ephedrine and N-methylephedrine with beta-cyclodextrin, heptakis(2,3-di-O-acety l) beta-cyclodextrin, heptakis(6-O-acetyl) beta-cyclodextrin. The stoi chiometry of the complexes formed between all three cyclodextrins and N-methylephedrine was found to be 1:1 by UV spectroscopy by means of t he Job technique. NMR spectra of the single enantiomers of ephedrine a nd N-methylephedrine in the presence of all three cyclodextrins gave i nformation about the parts of the ligands which interact differently w ith the host molecules and may be responsible for the chiral discrimin ation. To quantify the complex stabilities, binding constants were cal culated from the changes in the chemical shifts of the ligand signals upon complexation. Analyses of the coupling constants of both species showed that no significant conformational change occurs upon complexat ion. ROESY spectra of these optical isomers with all three cyclodextri ns provided detailed information about the geometry of the complexes. Different intermolecular cross-peaks between the individual isomers of ephedrine and N-methylephedrine were found for native beta-cyclodextr in and its 2,3-diacetylated derivative but not for 6-acetyl cyclodextr in. Analyses of the intramolecular cross-signals of the ligands confir med that no significant conformational change occurs upon complexation . Chirality 9:211-219, 1997. (C) 1997 Wiley-Liss, Inc.