American Chemical Society
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Determination of the Absolute Configuration of a Chiral Oxadiazol-3-one Calcium Channel Blocker, Resolved Using Chiral Chromatography, via Concerted Density Functional Theory Calculations of Its Vibrational Circular Dichroism, Electronic Circular Dichroism, and Optical Rotation

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journal contribution
posted on 2007-06-22, 00:00 authored by P. J. Stephens, F. J. Devlin, F. Gasparrini, A. Ciogli, D. Spinelli, B. Cosimelli
The chiral oxadiazol-3-one 2 has recently been shown to exhibit myocardial calcium entry channel blocking activity, substantially higher than that of diltiazem. To determine the enantioselectivity of this activity, the enantiomers of 2 have been resolved using chiral chromatography. The absolute configuration (AC) of 2 has been determined by comparison of density functional theory (DFT) calculations of its vibrational circular dichroism (VCD) spectrum, electronic circular dichroism (ECD) spectrum, and optical rotation (OR) to experimental VCD, ECD, and OR data. All three chiroptical properties yield identical ACs; the AC of 2 is unambiguously determined to be S(+)/R(−).