Concise Syntheses of Lycojapomine Alkaloids Enabled by Radical Dearomatization of a Pyrrole
Abstract
We disclose the first total syntheses of the complex alkaloids Lycojapomine A and B. Our synthetic strategy is built on a dearomatization and stepwise functionalization of a pyrrole starting material, constructing the three-dimensional structure of the target around it. This is enabled by a high-yielding photoinduced primary radical addition from the N-hydroxy phthalimide ester and a subsequent silver-catalyzed 5-endo-dig and Aza-silyl-Prins annulation cascade. Divergent control over an aldol reaction yields both Lycojapomines A and B in an efficient manner, without the need for any excess protecting groups.
Copyright and License
© 2025 American Chemical Society.
Acknowledgement
The NIH-NIGMS (R35GM145239), NSF (CHE-2247315), Heritage Medical Research Investigators Program, Bristol Myers Squibb (graduate fellowship to B.M.G.), and Caltech are thanked for the support of our research program. We gratefully acknowledge Dr. Scott Virgil and the Caltech Center for Catalysis and Chemical Synthesis for access to analytical equipment.
Supplemental Material
Materials and methods, abbreviations, reaction conditions, procedures, comparison, references, spectral data (PDF)
Files
ja5c05721_si_001.pdf
Additional details
Identifiers
- PMID
- 40489233
Related works
- Describes
- Journal Article: 40489233 (PMID)
Funding
- National Institute of General Medical Sciences
- R35GM145239
- National Science Foundation
- CHE-2247315
- Heritage Medical Research Investigators Program
- Bristol-Myers Squibb (United States)
- California Institute of Technology
Dates
- Submitted
-
2025-04-03
- Accepted
-
2025-06-02
- Available
-
2025-06-09Published
Caltech Custom Metadata
- Caltech groups
- Division of Chemistry and Chemical Engineering (CCE) , Heritage Medical Research Institute
- Publication Status
- Published