Department of Medicinal Chemistry & Pharmacognosy and Institute for Tuberculosis Research, College of Pharmacy, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
J Org Chem. 2013 Apr 5;78(7):2827-39. doi: 10.1021/jo302720h. Epub 2013 Mar 5.
This study demonstrates how regio- and diastereo-isomers with near-identical NMR spectra can be distinguished and unambiguously assigned using quantum mechanical driven (1)H iterative Full Spin Analysis (HiFSA). The method is illustrated with four natural products, the flavonolignans silybin A, silybin B, isosilybin A, and isosilybin B, which exhibit extremely similar coupling patterns and chemical shift differences well below the commonly reported level of accuracy of 0.01 ppm. The HiFSA approach generated highly reproducible (1)H NMR fingerprints that enable distinction of all four isomers at (1)H frequencies from 300 to 900 MHz. Furthermore, it is demonstrated that the underlying numeric (1)H NMR profiles, combined with iterative computational analysis, allow parallel quantification of all four isomers, even in difficult to characterize reference materials and mixtures. The results shed new light on the historical challenges to the qualitative and quantitative analysis of these therapeutically relevant flavonolignans and open new opportunities to explore hidden diversity in the chemical space of organic molecules.
本研究展示了如何使用量子力学驱动的（1）H 迭代全自旋分析（HiFSA）区分和明确分配具有几乎相同 NMR 光谱的区域和非对映异构体。该方法通过四个天然产物（黄酮木脂素）进行了说明，即水飞蓟宾 A、水飞蓟宾 B、异水飞蓟宾 A 和异水飞蓟宾 B，它们表现出非常相似的耦合模式和化学位移差异，远低于通常报道的 0.01 ppm 的精度水平。HiFSA 方法生成了高度可重复的（1）H NMR 指纹图谱，可在 300 至 900 MHz 的（1）H 频率下区分所有四种异构体。此外，还证明了基础数值（1）H NMR 图谱，结合迭代计算分析，即使在难以表征的参考材料和混合物中，也允许对所有四种异构体进行平行定量。这些结果为这些治疗相关黄酮木脂素的定性和定量分析带来了新的挑战，并为探索有机分子化学空间中的隐藏多样性开辟了新的机会。
