Synthesis of (−)-Picrotoxinin by Late-Stage Strong Bond Activation
Steven W. M. Crossley, Guanghu Tong, Michael J. Lambrecht, Hannah E. Burdge, Ryan A. Shenvi
Abstract
We report a concise, stereocontrolled synthesis of the neurotoxic sesquiterpenoid (−)-picrotoxinin (1, PXN). The brevity of the route is due to regio- and stereoselective formation of the [4.3.0] bicyclic core by incorporation of a symmetrizing geminal dimethyl group at C5. Dimethylation then enables selective C–O bond formation in multiple intermediates. A series of strong bond (C–C and C–H) cleavages convert the C5 gem-dimethyl group to the C15 lactone of PXN.
Topics & Concepts
ChemistryGeminalStereochemistryStereoselectivityBicyclic moleculeLactoneOrganic chemistryCatalysisAlkaloids: synthesis and pharmacologyBotulinum Toxin and Related Neurological DisordersChemical synthesis and alkaloids