NMR Studies of Drugs. Applications of Lanthanide Shift Reagents to Afloqualone,an Axially Chiral Quinazolinone. |
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| Authors: | Robert Rothchild Helen Wyss |
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| Institution: | 1. The City University of New York, John Jay College of Criminal Justice, Toxicology Research and Training Center, Science Department , 445 West 59th Street, New York, NY, 10019-1199;2. Doctoral Faculty , The Graduate School and University Center, The City University of New York |
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| Abstract: | The skeletal muscle relaxant, aflogualone, 1, has been studied by 1H NMR in CDC13 at 60 and 300 MHz in the presence of added chiral Eu(HFC)3] or achiral Eu(FOD)3] lanthanide shift reagents (LSR). With Eu(HFC)3, significant enantiomeric shift differences, ΔΔδ, can be induced for most of the nuclei of 1, with near-baseline resolution obtainable for the H-5 signals of each enantiomer, indicating excellent analytical potential for direct determination of enantiomeric excess of samples of 1. Observation of ΔΔδ directly confirms hindered rotation about the bond between N (3) and the 2-methylphenyl group, i.e., the N (sp2) - C(sp2) bond, leading to axial chirality in 1 with slow rotation on the NMR timescale. Assignments are supported by 2D COSY spectra at 300 MHz. Relative lanthanide-induced shift magnitudes for the protons of 1 are compared. |
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| Keywords: | H)-guinazolinone" target="_blank">6-Amino-2-(fluoromethyl)-3-(2-methylphenyl)-4(3H)-guinazolinone LSR Europium Eu(HFC)3 Eu(FOD)3 Muscle relaxant NMR shift reagents Hindered rotation Stereoisomers Enantiomeric excess Conformers Analysis One- and two-dimensional NMR COSY |
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