Stereochemical Research on Cembranes Diterpenoid Sinulariol Z Based on Residual Dipolar Couplings

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.

Keywords

• residual dipolar coupling (rdc)
• cembranes diterpenoids
• stereochemistry
• flexible macrocyclic molecules
• natural products