NMR Studies of Drugs. Applications of Achiral and Chiral Lanthanide Shift Reagents to Citiolone.

Abstract

The 200 MHz ¹H NMR spectra of citiolone, 1, have been studied in CDC1₃ solution at ambient temperatures with the achiral lanthanide shift reagent (LSR) tris (6, 6, 7, 7, 8, 8, 8-heptafluoro-2, 2-dimethyl-3, 5-octanedionato) europium (III), Eu (FOD)₃, 2, for spectral simplification, and with the chiral LSR, tris [3-heptafluoropropylhydroxymethylene)-(+)-camphorato] europium (III), Eu (HFC)₃, 3. With 3, substantial enantiomeric shift differences were obtained for the H-3, NH and CH₃CO resonances, with the H-3 signals essentially baseline resolved and free from overlaps with [3]/[1] molar ratios ca. 0.8–1.0. For the acetyl signal, valley heights as low as 4–5% were achieved between the signals of the antipodes when [3]/[1] ratios ca. 0.7–0.8 were used. These conditions should permit direct determinations of enantiomeric excess of 1.

Key Words:

• 2-Acetamido-4-mercaptobutyric acid γ-thiolactone
• N-acetylhomocysteinethiolactone
• Europium
• LSR
• Eu(FOD)₃
• Eu (HFC)₃
• Analysis
• Enantiomeric excess
• Stereoisomer