NMR-STUDIES OF DRUGS - PHENSUXIMIDE - H-1 AND C-13 NMR METHODS WITH CHIRAL SOLVATING AGENTS AND LANTHANIDE SHIFT-REAGENTS

NMR spectra of the racemic anticonvulsant, phensuximide, ($) under bar 1, in CDCl3 solution, have been studied with additives to explore met hods for potential direct determination of enantiomeric excess (% ee). Proton studies at 200 MHz with the chiral solvating agent (CSA) (-)-2 ,2,-trifluoro-1-(9-anthryl)ethanol (TFAE), ($) under bar 2, with ($) u nder bar 2:($) under bar 1 molar ratios up to 3.0, as well as runs wit h mixtures of ($) under bar 2 and the achiral lanthanide shift reagent (LSR), ,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato) europium(II I), ($) under bar 3, known as Eu(FOD)(3), were carried out. Additional NMR studies were performed with an added chiral LSR, pylhydroxymethyl ene)-(+)-camphorato]europium(III), ($) under bar 4, known as Eu(HFC)(3 ) or Eu(HFBC)(3), using H-1 NMR, and analogous runs with ($) under bar 4 examined the 50 MHz C-13 NMR. The latter appeared to offer good pro mise for ee determinations based on the resolution of signals of the e nantiomers of ($) under bar 1 for one of the carbonyl carbons with a ( $) under bar 4:($) under bar 1 molar ratio near 0.5, with valley heigh ts less than 12% being obtainable. Relative slopes of plots of lanthan ide-induced shifts (LIS) versus ($) under bar 4:($) under bar 1 ratios for the carbons of ($) under bar 1 are compared and discussed. Partia l C-13 NMR assignments were made based on these LIS slopes and on DEFT experiments.