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Efficient NMR spectroscopy approach for the determination of the relative configuration of Δ5,6Δ11,12-jatrophane
Wenjing Tian1, Jie Li1, Mi Zhou2
1Fujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China.
Phytochemistry
|June 11, 2025
Summary
This study isolated novel jatrophane diterpenes from Euphorbia helioscopia L. and developed an NMR strategy for configuration determination, revealing their potential as chemosensitizers by inhibiting CHK1 and Wee1 phosphorylation.
Area of Science:
- Natural Product Chemistry
- Organic Chemistry
- Medicinal Chemistry
Background:
- Jatrophane diterpenes, exclusive to the Euphorbiaceae family, possess a complex scaffold challenging for configuration determination via NOESY spectra.
- The high flexibility and variable conformers of the 5/12-fused ring core in jatrophane diterpenes complicate structural elucidation.
- Euphorbia helioscopia L. is a source of diverse macrocyclic diterpenes, including jatrophane-type compounds.
Purpose of the Study:
- To isolate and characterize jatrophane diterpenes from Euphorbia helioscopia L.
- To develop an efficient NMR spectroscopic strategy for determining the relative configurations of Δ5,6Δ11,12-jatrophane diterpenes.
- To evaluate the potential of isolated jatrophane diterpenes as chemosensitizers by assessing their inhibitory effects on CHK1 phosphorylation.
Main Methods:
- Phytochemical investigation and isolation of 36 macrocyclic diterpenes from Euphorbia helioscopia L.
- Structure elucidation using NMR spectroscopy and X-ray crystallography for key compounds.
- Western blotting assay to evaluate inhibitory effects against camptothecin (CPT)-induced CHK1 phosphorylation.
Main Results:
- Isolation of 36 macrocyclic diterpenes, including 34 jatrophane-type compounds, with one novel compound (1).
- Determination of relative configurations using an efficient NMR spectroscopic strategy based on a classification of 10 structural types.
- Compound 23 demonstrated enhanced chemosensitivity of MCF-7 cells to CPT by inhibiting CHK1 and Wee1 phosphorylation and inducing PARP cleavage.
Conclusions:
- A robust NMR strategy for determining jatrophane diterpene configurations was established.
- Jatrophane diterpenes show promise as chemosensitizer agents, enhancing tumor cell sensitivity to chemotherapy.
- Compound 23 offers a potential therapeutic lead for overcoming chemotherapy resistance.
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