Stephens P J, Devlin F J, Gasparrini F, Ciogli A, Spinelli D, Cosimelli B
Department of Chemistry, University of Southern California, Los Angeles, California 90089-0482, USA.
J Org Chem. 2007 Jun 22;72(13):4707-15. doi: 10.1021/jo070302k. Epub 2007 May 22.
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(-).
手性恶二唑-3-酮2最近已被证明具有心肌钙通道阻断活性，其活性大大高于地尔硫卓。为了确定这种活性的对映选择性，已使用手性色谱法拆分了2的对映体。通过将其振动圆二色性（VCD）光谱、电子圆二色性（ECD）光谱和旋光（OR）的密度泛函理论（DFT）计算结果与实验VCD、ECD和OR数据进行比较，确定了2的绝对构型（AC）。所有这三种手性光学性质都产生相同的AC；明确确定2的AC为S(+)/R(-)。
