NMR Studies of Drugs. Applications of Achiral and Chiral Lanthanide Shift Reagents to Acifran Methyl Ester. LSR Binding to a Multifunctional Substrate.

Abstract

Abstract The antihyperlipoproteinemic agent, acifran, has been studied as its racemic methyl ester, 1, by 60 MHz 1H NMR in CDC13 solution at 28±1° with the added achiral lanthanide shift reagent (LSR), tris(6, 6, 7, 7, 8, 8, 8-heptaf luoro-2, 2-dimethyl-3, 5-octanedionato-europium(III), Eu (FOD)3, 2, for spectral simplification, and with the chiral LSRs, tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorato]europium(III), Eu(HFC)3, 3, and tris[3-(trifluoromethylhydroxymethylene)-(+)-camphorato]europium(III), Eu (FACAM)3, 4, for potential determinations of enantiomeric excess. Relative lanthanide-induced shift (LIS) magnitudes with the three LSRs were interpreted as consistent with major lanthanide binding at the 4-oxo carbonyl, but contrasting behavior in observed enantiomeric shift differences (ΔΔδ) with 3 versus 4 may suggest different bound complex geometries for 3 or 4 with 1.