A Convergent Total Synthesis of (+)-Ineleganolide
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1.
California Institute of Technology
Abstract
We report the total synthesis of the furanobutenolide-derived diterpenoid (+)-ineleganolide. The synthetic approach relies on a convergent strategy based on the coupling of two enantioenriched fragments, which are derived from (−)-linalool and (+)-norcarvone, respectively. A high-yielding, one-step Michael addition and aldol cascade furnishes a pentacyclic framework as a single diastereomer, thereby overcoming previous challenges in controlling stereochemistry. The endgame features an O2-facilitated C–H oxidation and a samarium diiodide-induced semipinacol rearrangement to furnish the highly rigid central seven-membered ring.
Copyright and License
© 2023 American Chemical Society. This publication is licensed under CC-BY 4.0.
Acknowledgement
This communication is dedicated to Professor E. J. Corey in anticipation of his 95th birthday. The authors thank NIH (R35GM145239) and the Heritage Medical Research Institute Investigator Program. Work conducted by S. C. Virgil at the Caltech Center for Catalysis and Chemical Synthesis is supported by the Beckman Institute at Caltech. The authors thank David VanderVelde for NMR assistance and maintenance of the Caltech NMR facility and Dr. Michael Takase and the Caltech XRD facility for XRD assistance. The authors thank Dr. Nick Hafeman, Elliot Hicks, and Hao Yu for thoughtful discussion. The authors thank Prof. John L. Wood and Joseph P. Tuccinardi for graciously providing synthetic NMR data for 1. Special thanks to all of the students and postdocs who have worked on the ineleganolide project in the Stoltz lab over more than 20 years, especially Drs. Jennifer L. Roizen and Robert A. Craig II, whose Ph.D. theses paved the way for the completion of this synthesis.
Data Availability
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Experimental procedures and spectroscopic data (1H NMR, 13C NMR, IR, and HRMS) (PDF)
CCDC 2245068–2245070 contain the supplementary crystallographic data for this paper.
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Additional details
- ISSN
- 1520-5126
- Heritage Medical Research Institute
- National Institutes of Health
- R35GM145239
- California Institute of Technology
- Beckman Institute
- Caltech groups
- Heritage Medical Research Institute