Dipartimento di Chimica e Chimica Industriale, University of Pisa, Pisa, Italy.
Chirality. 2009;21 Suppl 1:E181-201. doi: 10.1002/chir.20795.
In this review article we examine state-of-the-art techniques for the structural elucidation of organic compounds isolated from natural sources. In particular, we focus on the determination of absolute configuration (AC), perhaps the most challenging but inevitable step in the whole process, especially when newly isolated compounds are screened for biological activity. Among the many methods employed for AC assignment that we review, special attention is paid to electronic circular dichroism (CD) and to the modern tools available for quantum-mechanics CD predictions, including TDDFT. In this context, we stress that conformational flexibility often poses a limit to practical CD calculations of solution CD spectra. Many crystalline natural products suitable for X-ray analysis do not contain heavy atoms for a confidential AC assignment by resonant scattering. However, their CD spectra can be recorded in the solid state, for example with the KCl pellet technique, and analyzed possibly by nonempirical means to provide stereochemical information. In particular, solid-state CD spectra can be compared with those calculated with TDDFT or other high-level methods, using the X-ray geometry as input. The solid-state CD/TDDFT approach, described in detail, represents a quick and reliable tool for AC assignment of natural products.
在这篇综述文章中，我们考察了从天然来源中分离出的有机化合物的结构解析的最新技术。特别是，我们关注绝对构型（AC）的确定，这可能是整个过程中最具挑战性但也是不可避免的一步，尤其是当新分离的化合物被筛选出具有生物活性时。在我们回顾的用于 AC 赋值的许多方法中，特别关注电子圆二色性（CD）以及用于量子力学 CD 预测的现代工具，包括 TDDFT。在这方面，我们强调构象灵活性通常对溶液 CD 光谱的实际 CD 计算构成限制。许多适合 X 射线分析的结晶天然产物不含重原子，因此无法通过共振散射进行可靠的 AC 赋值。然而，它们的 CD 光谱可以在固态下记录，例如使用 KCl 压片技术，并通过非经验方法进行分析，以提供立体化学信息。特别是，固态 CD 光谱可以与使用 X 射线几何形状作为输入的 TDDFT 或其他高级方法计算的光谱进行比较。详细描述的固态 CD/TDDFT 方法代表了一种快速可靠的天然产物 AC 赋值工具。
