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Updated: Jun 25, 2026
11:04
Preparation of Enantiopure Non-Activated Aziridines and Synthesis of Biemamide B, D, and epiallo-Isomuscarine
Published on: June 13, 2022
Asymmetric Total Synthesis of (+)-Acaulone B.
Sho Fujii1, Jun Hirabayashi1, Akira Katsuyama1,2
1Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
The Journal of Organic Chemistry
|June 23, 2026
Summary
Researchers synthesized Acaulone B using late-stage Diels-Alder reactions on a macrocycle. This method efficiently builds complex natural products by functionalizing large ring structures.
Area of Science:
- Natural Product Synthesis
- Organic Chemistry
- Computational Chemistry
Background:
- Acaulone B is a complex natural product isolated from *Acaulium* sp. H-JQSF.
- Synthesizing complex macrocyclic natural products remains a significant challenge in organic chemistry.
Purpose of the Study:
- To develop an efficient synthetic strategy for Acaulone B.
- To investigate the application of late-stage functionalization in macrocycle synthesis.
- To elucidate the mechanism and regioselectivity of the key Diels-Alder reaction.
Main Methods:
- Isolation of Acaulone B from *Acaulium* sp. H-JQSF.
- Chemo-, regio-, and stereoselective Diels-Alder reactions for constructing the cyclohexenone moiety.
- Density Functional Theory (DFT) calculations to analyze the regioselectivity of the cycloaddition.
Main Results:
- Successful synthesis of Acaulone B, incorporating a cyclohexenone through a Diels-Alder reaction.
- The Diels-Alder reaction proceeded with high chemo-, regio-, and stereoselectivity.
- DFT calculations confirmed the lowest Gibbs energy for the transition state (TS) structure, indicating an asynchronous cycloaddition pathway.
Conclusions:
- Late-stage functionalization of macrocycles is an effective strategy for synthesizing complex natural products like Acaulone B.
- The developed synthetic route highlights the power of Diels-Alder reactions in complex molecule construction.
- Computational analysis provided valuable insights into the reaction mechanism and selectivity.
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