Asymmetric Total Synthesis and Structural Reassignment of Nervione
Kunita Phakdeeyothin1, Jian-Liang Li2, Yi-Tian Hong3
1Institute of Chemistry, Academia Sinica, Taipei 11529, Taiwan.
The Journal of Organic Chemistry
|March 19, 2025
Summary
Optically active nervione, a natural product, was synthesized in both (+) and (-) forms. This study also corrected the absolute configuration of nervione based on circular dichroism (CD) spectra analysis.
Area of Science:
- Organic Chemistry
- Natural Product Synthesis
- Stereochemistry
Background:
- Nervione is a natural product first isolated from *Nervilia concolor* in 2022.
- The synthesis and absolute configuration of nervione were previously unestablished.
Purpose of the Study:
- To achieve the first asymmetric total synthesis of optically active nervione in both (+) and (-) forms.
- To reassign the absolute configuration of nervione.
- To establish a synthetic route for future studies on nervione's biological activity.
Main Methods:
- Asymmetric total synthesis utilizing commercially available resorcinol.
- Employing *ortho*-directed strategies for efficient synthesis.
- Utilizing Lewis acid-mediated, diastereoselective reduction for stereochemical control.
Main Results:
- Successful synthesis of optically pure nervione in both enantiomeric forms.
- A 10-step synthetic route was established.
- Circular dichroism (CD) spectra analysis led to the reassignment of nervione's absolute configuration.
Conclusions:
- The total synthesis of nervione in both (+) and (-) forms was achieved.
- The absolute configuration of nervione was reassigned from (3S, 8R) to (3R, 8S).
- This work provides a foundation for further research into nervione.
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