Synthesis of Picrotoxinin by Late Stage Strong Bond Activation.
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.
Journal of the American Chemical Society