Total Synthesis of Aleutianamine
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1.
California Institute of Technology
Abstract
Aleutianamine is a recently isolated pyrroloiminoquinone natural product that displays potent and selective biological activity toward human pancreatic cancer cells with an IC₅₀ of 25 nM against PANC-1, making it a potential candidate for therapeutic development. We report a synthetic approach to aleutianamine wherein the unique [3.3.1] ring system and tertiary sulfide of this alkaloid were constructed via a novel palladium-catalyzed dearomative thiophene functionalization. Other highlights of the synthesis include a palladium-catalyzed decarboxylative pinacol-type rearrangement of an allylic carbonate to install a ketone and a late-stage oxidative amination. This concise and convergent strategy will enable access to analogues of aleutianamine and further investigation of the biological activity of this unique natural product.
Copyright and License
This publication is licensed under CC-BY-NC-ND 4.0.
Acknowledgement
The authors gratefully acknowledge Caltech, the NSF (CHE-2247315), and the Heritage Medical Research Investigators Program for financial support. Z.P.S. and S.P.R. thank the NSF GRFP for predoctoral fellowships. Dr. Mike Takase (Caltech) and Dr. Mona Shahgholi (Caltech) are thanked for assistance with X-ray crystallography and mass spectrometry, respectively. Dr. David VanderVelde (Caltech) is acknowledged for NMR instrumentation.
Contributions
H.Y. and Z.P.S. contributed equally.
Conflict of Interest
The authors declare no competing financial interest.
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Additional details
- ISSN
- 1520-5126
- PMCID
- PMC10690800
- National Science Foundation
- CHE-2247315
- California Institute of Technology
- Heritage Medical Research Institute
- National Science Foundation
- Graduate Research Fellowship
- Caltech groups
- Heritage Medical Research Institute