Lancefield Christopher S, Slawin Alexandra M Z, Westwood Nicholas J, Lebl Tomas
School of Chemistry and Biomedical Sciences Research Complex, University of St Andrews and EaStCHEM, North Haugh, St Andrews, KY16 9ST, UK.
Magn Reson Chem. 2015 Jun;53(6):467-75. doi: 10.1002/mrc.4213. Epub 2015 Apr 9.
Determining the conformational preferences of molecules in solution remains a considerable challenge. Recently, the use of residual dipolar coupling (RDC) analysis has emerged as a key method to address this. Whilst to date the majority of the applications have focused on biomolecules including proteins and DNA, the use of RDCs for studying small molecules is gaining popularity. Having said that, the method continues to develop, and here, we describe an early case study of the quantification of conformer populations in small molecules using RDC analysis. Having been inspired to study conformational preferences by unexpected differences in the NMR spectra and the reactivity of related natural products, we showed that the use of more established techniques was unsatisfactory in explaining the experimental observations. The use of RDCs provided an improved understanding that, following use of methods to quantify conformer populations using RDCs, culminated in a rationalisation of the contrasting diastereoselectivities observed in a ketone reduction reaction.
确定溶液中分子的构象偏好仍然是一项巨大的挑战。最近，残余偶极耦合（RDC）分析的应用已成为解决这一问题的关键方法。虽然迄今为止大多数应用都集中在包括蛋白质和DNA在内的生物分子上，但RDC用于研究小分子的应用正越来越受欢迎。话虽如此，该方法仍在不断发展，在此，我们描述了一个早期案例研究，即使用RDC分析对小分子中的构象异构体群体进行定量。受相关天然产物的NMR光谱和反应性中意外差异的启发，我们开始研究构象偏好，结果表明，使用更成熟的技术无法令人满意地解释实验观察结果。RDC的使用提供了更好的理解，在使用RDC定量构象异构体群体的方法之后，最终对酮还原反应中观察到的对比非对映选择性进行了合理化解释。
