Total synthesis of (−)-scabrolide A and (−)-yonarolide
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1.
California Institute of Technology
Abstract
The complete account of the total syntheses of scabrolide A and yonarolide is disclosed. This article describes an initial approach involving a bio-inspired macrocyclization/transannular Diels–Alder cascade, which ultimately failed due to undesired reactivity during macrocycle construction. Next, the evolution of a second and third strategy, which both involve an initial intramolecular Diels–Alder reaction followed by a late-stage closure of the seven-membered ring of scabrolide A are detailed. The third strategy was first validated on a simplified system, but problems were encountered during a key [2 + 2] photocycloaddition on the fully elaborated system. An olefin protection strategy was employed to circumvent this problem, ultimately leading to the completion of the first total synthesis of scabrolide A and the closely related natural product yonarolide.
Additional Information
This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. The authors wish to thank NSF (CHE1800511), NIH (R35GM 145239), and the Heritage Medical Research Investigators Program for funding. Additionally, B. P. P. thanks NSF for support in the form of a predoctoral fellowship. The authors thank Dr David VanderVelde for NMR assistance and maintenance of the Caltech NMR facility, Dr Michael Takase and the Caltech XRD facility for XRD assistance, and Dr Mona Shahgholi for mass spectrometry assistance. The authors thank the Beckman Institute for their support of the Caltech XRD facility as well as the Dow Next Generation Instrument Grant. All publication charges for this article have been paid for by the Royal Society of Chemistry. Author contributions. N. J. H., S. A. L., C. E. R., B. P. P., and S. C. V. conceived of and performed experiments. B. M. S. supported and supervised the research. N. J. H. wrote the original draft of the manuscript, which was edited by all authors. There are no conflicts of interest to declare.Attached Files
Published - d3sc00651d.pdf
Supplemental Material - d3sc00651d1.pdf
Supplemental Material - d3sc00651d2.cif
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Additional details
- PMCID
- PMC10173254
- Eprint ID
- 122080
- Resolver ID
- CaltechAUTHORS:20230630-537205000.3
- CHE-1800511
- NSF
- R35GM145239
- NIH
- Heritage Medical Research Institute
- NSF Graduate Research Fellowship
- Caltech Beckman Institute
- Dow Next Generation Educator Fund
- Created
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2023-07-01Created from EPrint's datestamp field
- Updated
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2023-07-01Created from EPrint's last_modified field
- Caltech groups
- Heritage Medical Research Institute