NMR Studies of Hindered Rotations in Drugs. Use of Achiral and Chiral Lanthanide Shift Reagents with Mecloqualone,an Axially Chiral Drug of Abuse. Rigorous Definition of Spin Systems. |
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| Authors: | Ronnie Benshafrut Kevin Bynum Robert Rothchild |
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| Institution: | 1. The Hebrew University of Jerusalem, Department of Organic Chemistry , Givat Ram, Jerusalem, Israel , 91904;2. The City University of New York, John Jay College of Criminal Justice, Science Department , 445 West 59th Street, New York, NY, 10019-1128;3. The Doctoral Faculty , The Graduate School and University Center , City University of, New York |
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| Abstract: | The axially chiral sedative/hypnotic drug of abuse, mecloqualone, 1, has been studied in CDC13 by 1H NMR at 60 and 300 MHz with the added achiral lanthanide shift reagent (LSR), tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5- octanedionato)europium(III), 2, and the chiral LSR, tris3-(heptafluoropropylhydroxymethylene)-(+)-camphorato] europium-(III), 3. Rigorous distinctions between the two (CH)4 spin systems of 1 with added 2 or 3 were achieved by two-dimensional homonuclear chemical shift correlation spectroscopy, COSY. Substantial up field (“anomalous”) shifts were observed for several nuclei of 1 with each LSR. Use of the chiral 3 elicited enantiomeric shift differences with baseline separations for several nuclei that should permit direct determinations of enantiomeric excess. COSY spectra allow determination of the relative sense of magnetic nonequivalence of selected nuclei of 1 with 3. |
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| Keywords: | Dynamic NMR One- and two-dimensional NMR COSY Restricted rotation Stereochemistry Enantiomers Sedative/hypnotics Eu(FOD)3 Eu(HFC)3 |
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