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Updated: Jun 21, 2025
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Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
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Total Synthesis of (±)-Baphicacanthcusine A Enabled by Sequential Ring Contractions
Paul P Sinclair1, Richmond Sarpong1
1Department of Chemistry, University of California, Berkeley, Berkeley, California, 94720, United States.
Angewandte Chemie (International Ed. in English)
|July 12, 2024
Summary
This study reports the first total synthesis of baphicacanthcusine A, a complex natural product. The novel synthesis features diastereoselective methods for creating pseudoindoxyl structures, paving the way for related alkaloid synthesis.
Area of Science:
- Organic Chemistry
- Natural Product Synthesis
- Medicinal Chemistry
Background:
- Baphicacanthcusine A is a poly-pseudoindoxyl natural product with potential biological activity.
- The complex structure of baphicacanthcusine A presents a significant synthetic challenge.
- Previous synthetic efforts have not achieved the total synthesis of this compound.
Purpose of the Study:
- To achieve the first total synthesis of baphicacanthcusine A.
- To develop novel synthetic methodologies for constructing poly-pseudoindoxyl alkaloids.
- To explore the chemical space around baphicacanthcusine A for potential drug discovery.
Main Methods:
- Leveraging oxidative rearrangement of indoles to pseudoindoxyls.
- Employing an acid-mediated cyclization/indole transposition.
- Utilizing diastereoselective oxidative ring contractions and site-selective C-H oxygenation.
Main Results:
- Successful completion of the first total synthesis of baphicacanthcusine A.
- Demonstration of a diastereoselective method for installing vicinal pseudoindoxyl heterocycles.
- Identification of a hidden symmetry element guiding the synthesis of oxidation precursors.
Conclusions:
- The developed synthetic strategy provides a robust foundation for accessing baphicacanthcusine A and related poly-pseudoindoxyl alkaloids.
- This work expands the synthetic toolkit for natural product synthesis.
- The synthetic route may enable further biological evaluation of baphicacanthcusine A and its analogs.
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