基于残留偶极耦合对西松烷二萜化合物sinulariol Z立体化学的研究

doi:10.11938/cjmr20243097

摘要/Abstract

摘要：

天然产物的立体化学研究，特别是柔性大环分子化合物的立体化学问题，一直是相关领域面临的巨大难题．西松烷二萜类化合物是一类典型的柔性大环分子化合物，采用耦合常数（Coupling constant）和NOE（Nuclear Overhauser effect）效应两种局部特性核磁共振参数来确定该类化合物立体构型是最常用的方法之一．残留偶极耦合（Residual dipolar coupling，RDC）和量子化学计算等方法的发展进一步丰富了解决立体化学问题的手段．其中，RDC作为一种非局部特性核磁共振参数，不仅被多次报道应用于蛋白质、核酸等生物分子的结构构建及功能研究，也逐渐被应用于许多天然产物分子的立体构型确定，在药物分子构型研究方面做出了突出贡献．目前，RDC在西松烷二萜类化合物的立体构型确定方面的研究报道较少．本文首次采用RDC参数探索西松烷二萜类化合物sinulariol Z的立体化学构型问题，并结合单晶X射线衍射法，对sinulariol Z的立体构型进行了再次确证，进一步验证了RDC参数在西松烷二萜类化合物立体化学研究中的可行性．

关键词: 残留偶极耦合参数, 西松烷二萜, 立体化学, 柔性大环分子, 天然产物

Abstract:

Research on the stereochemistry of natural products, especially that of flexible macrocyclic molecules, has always been a huge challenge. Cembranes diterpenoids are a typical class of flexible macrocyclic molecules, whose configurations are often determined by coupling constant and nuclear Overhauser effect (NOE), both of which are nuclear magnetic resonance (NMR) parameters with local character. The development of methods such as residual dipolar coupling (RDC) and quantum chemical calculations has further expanded the toolbox for solving stereochemical problems. RDC, as an NMR parameter with non-local character, has not only been reported in the structure construction and function research of biomolecules such as proteins and nucleic acids, but has also gradually been applied to the configuration determination of natural products, contributing significantly to the stereochemical research on drug molecules. At present, there are few reports of RDC application in determining the configurations of cembranes diterpenoids. Here, the stereochemical configuration of sinulariol Z is investigated by RDC for the first time and confirmed by X-ray diffraction, further demonstrating the feasibility of RDC in the stereochemical study on cembranes diterpenoids.

Key words: residual dipolar coupling (RDC), cembranes diterpenoids, stereochemistry, flexible macrocyclic molecules, natural products

中图分类号:

O482.53

石星, 张越, 张秀丽, 王聪. 基于残留偶极耦合对西松烷二萜化合物sinulariol Z立体化学的研究[J]. 波谱学杂志, 2024, 41(3): 322-330.

SHI Xing, ZHANG Yue, ZHANG Xiuli, WANG Cong. Stereochemical Research on Cembranes Diterpenoid Sinulariol Z Based on Residual Dipolar Couplings[J]. Chinese Journal of Magnetic Resonance, 2024, 41(3): 322-330.

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Position	Sinulariol Z
Position	Exp. ¹D_CH/Hz	Calc. ¹D_CH/Hz (SSSR)
C2-H2	8.104	8.74
C3-H3	10.54	9.49
C6-H6a	-16.524	-10.51
C9-H9a	0.79	3.24
C9-H9b	-1.346	1.96
C11-H11	9.572	10.15
C15-H15	1.614	3.53
C16-H16	-0.92	1.63
C17-H17	0.572	0.34
C18-H18	-3.562	-1.93
C19-H19	2.486	2.93
C20-H20	-2.15	-2.08