Chiral analysis of pantolactone with molecular rotational resonance spectroscopy
Chiral analysis of pantolactone with molecular rotational resonance spectroscopy
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DOI：
10.1002/chir.23379
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发表时间：
2021-10-26
期刊：
影响因子：
2
通讯作者：
Pate, Brooks H.
中科院分区：
文献类型：
--
作者：
Sonstrom, Reilly E.;Neill, Justin L.;Pate, Brooks H.
建立了一种测定泛酸和泛醇合成中间体泛内酯对映体过量的分子旋转共振光谱方法。通过与小的手性标签分子络合来区分对映异构体，所述小的手性标签分子在用于将样品注入光谱仪的脉冲喷射膨胀中产生非对映异构体络合物。这些配合物具有不同的惯性矩，因此它们的光谱可通过MRR光谱解析。定量对映体过量（EE）测量通过当使用高的已知EE的手性标签样品时取归一化的络合物信号水平的比率来进行，而样品的绝对构型可以从络合物几何形状的电子结构计算来确定。这些测量可以在不需要已知对映体纯度的参比样品的情况下进行。在分析中使用了两种仪器。一个宽带，啁啾脉冲光谱仪是用来执行复杂的结构表征。宽带光谱仪也用于确定EE;然而，这种方法需要相对较长的测量时间。目标MRR光谱仪也用于演示EE分析，样品到样品的循环时间约为15分钟。通过与手性气相色谱法进行比较，并通过测量由已知EE的（R）-泛内酯和（S）-泛内酯样品混合物制备的一系列参比样品，证明了该方法的定量准确度。
A molecular rotational resonance spectroscopy method for measuring the enantiomeric excess of pantolactone, an intermediate in the synthesis of panthenol and pantothenic acid, is presented. The enantiomers are distinguished via complexation with a small chiral tag molecule, which produces diastereomeric complexes in the pulsed jet expansion used to inject the sample into the spectrometer. These complexes have distinct moments of inertia, so their spectra are resolved by MRR spectroscopy. Quantitative enantiomeric excess (EE) measurements are made by taking the ratio of normalized complex signal levels when a chiral tag sample of high, known EE is used, while the absolute configuration of the sample can be determined from electronic structure calculations of the complex geometries. These measurements can be performed without the need for reference samples with known enantiopurity. Two instruments were used in the analysis. A broadband, chirped-pulse spectrometer is used to perform structural characterization of the complexes. The broadband spectrometer is also used to determine the EE; however, this approach requires relatively long measurement times. A targeted MRR spectrometer is also used to demonstrate EE analysis with approximately 15-min sample-to-sample cycle time. The quantitative accuracy of the method is demonstrated by comparison with chiral gas chromatography and through the measurement of a series of reference samples prepared from mixtures of (R)-pantolactone and (S)-pantolactone samples of known EE.