Asymmetric Total Synthesis of (−)-Crotonine G and (−)-Crotonolide D
-
1.
California Institute of Technology
Abstract
The first enantioselective total syntheses of crotonine G and crotonolide D are disclosed. The synthetic approach employs a SmI2 mediated ketyl radical cyclization to form the highly congested quaternary carbon at the center of these complex molecules. Following the furan introduction, the core structure of the natural product is constructed via oxidative olefin cleavage to install the unusual C-19 and C-20 oxidation. Finally, palladium-catalyzed carbonylation, furan oxidation and acid mediated condensation/epimerization complete the synthesis.
Copyright and License
© 2025 American Chemical Society.
Acknowledgement
The authors gratefully acknowledge NIH-NIGMS (R35GM145239), Caltech, the Heritage Medical Research Investigators Program for financial support. Work conducted by S.C.V. at the Caltech Center for Catalysis and Chemical Synthesis is supported by the Beckman Institute at Caltech. Dr. Mike Takase (Caltech) is thanked for assistance with X-ray crystallography. Dr. David VanderVelde (Caltech) is acknowledged for NMR instrumentation. We thank the Caltech High Performance Computing Center for support. P.C. would like to thank the NSF GRFP for funding. Y.H. would like to thank the JSPS Overseas Challenge Program for Young Researchers. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. The authors thank Benjamin Gross and Elliot Hicks for thoughtful discussion.
Supplemental Material
Computed structures (ZIP)
QM energies (XLSX)
Experimental procedures, spectroscopic data (1H NMR, 13C NMR, IR, HRMS), and crystallographic data (PDF)
Data Availability
Deposition Numbers 2448227 and 2448229–2448230 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via the joint Cambridge Crystallographic Data Centre (CCDC) and Fachinformationszentrum Karlsruhe Access Structures service.
Files
ja5c07585_si_003.pdf
Additional details
Funding
- National Institute of General Medical Sciences
- R35GM145239
- California Institute of Technology
- Heritage Medical Research Institute
- National Science Foundation Graduate Research Fellowship Program
Caltech Custom Metadata
- Caltech groups
- Division of Chemistry and Chemical Engineering (CCE)
- Publication Status
- Published