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PXN ChemRxiv.pdf (1.7 MB)

Total Synthesis of (–)-Picrotoxinin

preprint
submitted on 06.08.2019, 20:56 and posted on 07.08.2019, 19:17 by Steven W. M. Crossley, Guanghu Tong, Michael J. Lambrecht, Hannah E. Burdge, Ryan Shenvi
We report a concise, stereocontrolled synthesis of the neurotoxic sesquiterpenoid, (–)-picrotoxinin (1, PXN). The brevity of the route owes to regio- and stereoselective formation of the [4.3.0] bicyclic core by incorporation of a symmetrizing geminal dimethyl group at C5. A series of strong C–C and C–H bond oxidations convert the C5 gem-dimethyl group to the C15 lactone of PXN. This counterintuitive strategy features the first example of demethylation (C–C bond cleavage) in total synthesis.

Funding

GM122606

PGS D3

JITRI Fellowship

A.O. Beckman Postdoctoral Fellowship

History

Email Address of Submitting Author

rshenvi@scripps.edu

Institution

The Scripps Research Institute

Country

United States of America

ORCID For Submitting Author

0000-0001-8353-6449

Declaration of Conflict of Interest

No conflict

Exports

ChemRxiv

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