Abstract: The stereochemistry of natural products has always been a huge challenge in some fields, especially the stereochemistry of flexible macrocyclic molecules. And as a typical class of flexible macrocyclic molecules, the configurations of cembranes diterpenoids 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 enriched the tools for solving stereochemical problems. Among them, RDC, as an NMR parameter with non-local character, has not only been reported to 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. This method has made a significant contribution to the stereochemical research on drug molecules. At present, there are fewer reports that the configurations of cembranes diterpenoids are determined by RDC. Here, the stereochemical configuration of sinulariol Z was 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