These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
Total Synthesis of (–)-Picrotoxinin
preprintsubmitted 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.