Collective Total Synthesis of Ergot Alkaloids
Fuye Wang1, Botao Bao1, Li Yang1
1Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, Yunnan Characteristic Plant Extraction Laboratory, School of Pharmacy, Yunnan University, Kunming, Yunnan 650500, P. R. China.
Organic Letters
|March 31, 2026
Summary
Researchers synthesized nine tetracyclic ergot alkaloids using a novel strategy. This work marks the first total synthesis of isopenniclavine and roquefortine A, expanding the chemical space of these bioactive natural products.
Area of Science:
- Organic Chemistry
- Natural Product Synthesis
- Medicinal Chemistry
Background:
- Ergot alkaloids are a class of bioactive natural products characterized by a tetrahydrobenzo[cd]indole core.
- These compounds exhibit diverse pharmacological activities, making them targets for chemical synthesis and drug discovery.
Purpose of the Study:
- To develop a collective total synthesis strategy for nine tetracyclic ergot alkaloids.
- To achieve the first-time synthesis of specific ergot alkaloids, namely isopenniclavine and roquefortine A.
Main Methods:
- A structural unit-oriented approach was employed for the synthesis.
- Key transformations included vinylogous arylation, intramolecular diastereoselective vinylogous Mannich reaction, and Mannich cyclization/reductive N-methylation.
Main Results:
- Successfully synthesized nine tetracyclic ergot alkaloids.
- Achieved the first total synthesis of isopenniclavine and roquefortine A.
- Established a robust strategy for constructing the ergoline core and its derivatives.
Conclusions:
- The developed synthetic strategy is efficient for accessing complex tetracyclic ergot alkaloids.
- This work provides access to previously unsynthesized ergot alkaloids, enabling further biological evaluation.
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