Department of Chemistry, Federal University of São Carlos-UFSCar, Rod. Washington Luis s/n, km 235, São Carlos, SP 13565-905, Brazil.
Institute of Science and Technology, Federal University of São Paulo-UNIFESP, R. Talim 330, São José dos Campos, SP 12231-280, Brazil.
Molecules. 2018 Feb 23;23(2):492. doi: 10.3390/molecules23020492.
Chiral natural product molecules are generally assumed to be biosynthesized in an enantiomerically pure or enriched fashion. Nevertheless, a significant amount of racemates or enantiomerically enriched mixtures has been reported from natural sources. This number is estimated to be even larger since the enantiomeric purity of secondary metabolites is rarely checked in the natural product isolation pipeline. This latter fact may have drastic effects on the evaluation of the biological activity of chiral natural products. A second bottleneck is the determination of their absolute configurations. Despite the widespread use of optical rotation and electronic circular dichroism, most of the stereochemical assignments are based on empirical correlations with similar compounds reported in the literature. As an alternative, the combination of vibrational circular dichroism and quantum chemical calculations has emerged as a powerful and reliable tool for both conformational and configurational analysis of natural products, even for those lacking UV-Vis chromophores. In this review, we aim to provide the reader with a critical overview of the occurrence of enantiomeric mixtures of secondary metabolites in nature as well the best practices for their detection, enantioselective separation using liquid chromatography, and determination of absolute configuration by means of vibrational circular dichroism and density functional theory calculations.
手性天然产物分子通常被认为是以对映体纯或富集的方式生物合成的。然而，从天然来源中已经报道了相当数量的外消旋体或对映体富集的混合物。由于在天然产物分离过程中很少检查次生代谢物的对映体纯度，因此这个数字估计更大。后一个事实可能会对手性天然产物生物活性的评估产生重大影响。第二个瓶颈是确定它们的绝对构型。尽管广泛使用旋光和电子圆二色性，但大多数立体化学分配是基于与文献中报道的类似化合物的经验相关性。作为替代方案，振动圆二色性和量子化学计算的结合已经成为分析天然产物构象和构型的强大可靠工具，即使对于那些缺乏紫外可见发色团的天然产物也是如此。在这篇综述中，我们旨在为读者提供对次生代谢物对映体混合物在自然界中存在的批判性概述，以及检测、使用液相色谱进行对映选择性分离以及通过振动圆二色性和密度泛函理论计算确定绝对构型的最佳实践。
