Published July 6, 2018
| Version Accepted Version + Supplemental Material
Journal Article
Open
Wolff/Cope Approach to the AB Ring of the Sesterterpenoid Variecolin
Creators
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1.
Bucknell University
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2.
Cipla (United States)
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3.
Lundbeck (Denmark)
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4.
California Institute of Technology
Abstract
A stereoselective synthesis of the AB ring of the complex sesterterpenoid variecolin is presented. Our strategy features the development of a tandem Wolff/Cope rearrangement of α-diazo cyclobutyl ketones for the construction of fused, 8-membered carbocycles. Preliminary studies revealed a facile Wolff rearrangement but a difficult vinyl ketene cyclobutane Cope rearrangement. We have leveraged an efficient microwave-promoted tandem rearrangement to prepare the desired functionalized cyclooctadienones that we envision as potential key intermediates in the convergent synthesis of variecolin.
Additional Information
© 2018 American Chemical Society. Received: November 22, 2017; Published: January 4, 2018. Special Issue: Synthesis of Antibiotics and Related Molecules. The authors thank the NIH-NIGMS (R01GM080269), Eli Lilly (predoctoral fellowship to M.R.K.), the Danish Council for Independent Research/Natural Sciences (postdoctoral fellowship to T.J.), Amgen, AbbVie, Bristol-Myers Squibb, Boehringer-Ingelheim, Merck, and Caltech for generous financial support. Dr. Takeharu Toyoshima and Angela Guerrero are acknowledged for contributions to substrate preparation and reaction scouting. Drs. David VanderVelde and Scott Ross of the Caltech NMR facility are thanked for invaluable assistance with NMR experiments and helpful discussions. Lawrence Henling and Michael Day are gratefully acknowledged for X-ray crystallographic structural determination. Dr. Mona Shahgholi and Naseem Torian are acknowledged for assistance with high-resolution mass spectrometry. The authors declare no competing financial interest.Attached Files
Accepted Version - nihms945199.pdf
Supplemental Material - jo7b02972_si_001.pdf
Supplemental Material - jo7b02972_si_002.cif
Files
jo7b02972_si_001.pdf
Additional details
Identifiers
- PMCID
- PMC6035096
- Eprint ID
- 84082
- Resolver ID
- CaltechAUTHORS:20180104-140230299
Funding
- NIH
- R01GM080269
- Eli Lilly
- Danish Council for Independent Research-Natural Sciences
- Amgen
- AbbVie
- Bristol-Myers Squibb
- Boehringer-Ingelheim
- Merck
- Caltech
Dates
- Created
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2018-01-04Created from EPrint's datestamp field
- Updated
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2022-03-18Created from EPrint's last_modified field