Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
Molecular Spectroscopy (MolSpec), Department of Chemistry, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium.
Molecules. 2022 Dec 26;28(1):214. doi: 10.3390/molecules28010214.
Structural elucidation has always been challenging, and misassignment remains a stringent issue in the field of natural products. The growing interest in discovering unknown, complex natural structures accompanies the increasing awareness concerning misassignments in the community. The combination of various spectroscopic methods with molecular modeling has gained popularity in recent years. In this work, we demonstrated, for the first time, its power to fully elucidate the 2-dimensional and 3-dimensional structures of two epimers in an epimeric mixture of 6-hydroxyhippeastidine. DFT calculation of chemical shifts was first performed to assist the assignment of planar structures. Furthermore, relative and absolute configurations were established by three different ways of computer-assisted structure elucidation (CASE) coupled with ORD/ECD/VCD spectroscopies. In addition, the significant added value of OR/ORD computations to relative and absolute configuration determination was also revealed. Remarkably, the differentiation of two enantiomeric scaffolds (crinine and haemanthamine) was accomplished via OR/ORD calculations with cross-validation by ECD and VCD.
结构解析一直具有挑战性，在天然产物领域，错误分配仍然是一个严峻的问题。随着人们对发现未知复杂天然结构的兴趣日益浓厚，对该领域中错误分配的认识也在不断提高。近年来，各种光谱方法与分子建模的结合已经越来越受欢迎。在这项工作中，我们首次展示了它在解析 6-羟基海罂粟碱差向异构体混合物中两个差向异构体的二维和三维结构方面的强大功能。首先进行了 DFT 计算化学位移，以协助平面结构的分配。此外，通过三种不同的计算机辅助结构解析（CASE）方法与 ORD/ECD/VCD 光谱学相结合，确定了相对和绝对构型。此外，还揭示了 OR/ORD 计算在相对和绝对构型确定方面的重要附加价值。值得注意的是，通过 OR/ORD 计算并通过 ECD 和 VCD 进行交叉验证，实现了两种对映体支架（血根碱和血根胺）的区分。
