Vicinal Bis(methylene) Heterocyclic Diene in Natural Product Synthesis: A Convergent Biomimetic Total Synthesis of
Michal Kadaník1, Ekaterina Frantsuzova1, Petr Matouš1
1Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy, Charles University, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
Abstract:
The first total syntheses of the natural isocoumarin prunolactone A with a 6/6/6/6/6 spiropentacyclic skeleton and its unnatural (3'R)-epimer in 10 and 8 steps, respectively, are reported. The syntheses feature in situ generation of a reactive 3,4-bis(methylene)isocoumarin intermediate, its biomimetic Diels-Alder reactions with the shikimic-acid-derived scytolide and (8R)-scytolide, and a Mitsunobu reaction allowing access to scytolide in a stereochemically pure form. Computational support for the selectivity of the Diels-Alder reaction is provided.
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