Total Synthesis of Eudesmanolides Alantolactone, Isoalantodiene, Alloalantolactone, and 5α,6α-Epoxyalantolactone
We report a 13-step total synthesis of the sesquiterpenoid lactone alantolactone and the first total syntheses of isoalantodiene, alloalantolactone, and 5α,6α-epoxyalantolactone. Key steps feature the intramolecular Diels–Alder cycloaddition of furan with an unactivated 1,1-disubstituted alkene to establish a quaternary carbon center, a palladium-catalyzed α-alkenylation of ketene silyl acetals, and a strain-promoted isomerization of a complex oxabicycle. We also describe the first enantioselective approach to this class of natural products.
Authors
- Kevin G. M. Kou (ORCID: https://orcid.org/0000-0002-4676-8846)
- Veronica Carta (ORCID: https://orcid.org/0000-0001-8089-8436)
- Justin D. DeBow (ORCID: https://orcid.org/0009-0006-1105-5009)
- Julio Manuel Larach
- Sarosh Abraham
- Anthony J Stevens (ORCID: https://orcid.org/0009-0003-5120-1670)
Institutions
- University of California, Riverside (US)
Publication Details
- Journal
- ChemRxiv
- Published
- 2025-08-29
- DOI
- https://doi.org/10.26434/chemrxiv-2025-694w3
- Primary Topic
- Natural product bioactivities and synthesis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- U.S. Department of Education
- Pfizer
- National Institutes of Health
- Directorate for Mathematical and Physical Sciences
- National Institute of General Medical Sciences
- Division of Chemistry