1H NMR studies of drugs with achiral and chiral lanthanide shift reagents: applications to the anticonvulsant pheneturide.
The anticonvulsant pheneturide, PNT, has been studied by 300 MHz 1H NMR in CDCl3 at ambient temperatures with the achiral lanthanide shift reagent (LSR) Eu(FOD)3, and with the chiral LSR, Eu(HFC)3. Both LSRs produced spectral simplification of the aryl proton signal region, and substantial lanthanide-induced shifts (LIS). With added Eu(HFC)3, enantiomeric shift differences (DeltaDeltadelta) were induced for most nuclei of PNT, indicating substantial potential for direct determination of enantiomeric excess. Valley heights between corresponding signals in the PNT enantiomers as low as 3.6% were achieved for the meta resonance. Least squares line-fitting was applied to the variation of chemical shift vs. [LSR]/[PNT] molar ratios for both LSRs. Tentative assignments were made for the NH absorptions based on two-dimensional NMR (COSY45), as well as their relative magnitudes of LIS, DeltaDeltadelta, and lanthanide-induced line broadening. The PNT conformation reported in the crystal is believed to be retained in solution with added LSR. The relative senses of magnetic nonequivalence were found to be the same among the three sets of aryl protons, and among the three kinds of protons in the ethyl moiety, with high levels of added chiral LSR, using 2D NMR.
Byrne
B
B
The City University of New York, John Jay College of Criminal Justice, Science Department, New York, New York 10019-1128, USA.
Rothchild
R
R
D000927:Anticonvulsants / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008674:Metals, Rare Earth / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry
D000927:Anticonvulsants; D007202:Indicators and Reagents; D008674:Metals, Rare Earth; C005825:pheneturide; D014508:Urea