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Synthesis of (-)-Picrotoxinin by Late-Stage Strong Bond Activation.

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.

SUBMITTER: Crossley SWM

PROVIDER: S-EPMC8011636 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Synthesis of (-)-Picrotoxinin by Late-Stage Strong Bond Activation.

Crossley Steven W M SWM Tong Guanghu G Lambrecht Michael J MJ Burdge Hannah E HE Shenvi Ryan A RA

Journal of the American Chemical Society 20200623 26

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. ...[more]

PMID: 32573211

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