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Published on: June 21, 2018
Total syntheses of (+)-zampanolide and (+)-dactylolide exploiting a unified strategy
Amos B Smith1, Igor G Safonov, R Michael Corbett
1Contribution from the Department of Chemistry, Monell Chemical Senses Center, and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104. smithab@sas.upenn.edu
Abstract:
The first total syntheses of (+)-zampanolide (1) and (+)-dactylolide (2), members of a new class of tumor cell growth inhibitory macrolides, have been achieved. Key features of the unified synthetic scheme included the stereocontrolled construction of the cis-2,6-disubstituted tetrahydropyran via a modified Petasis-Ferrier rearrangement, a highly convergent assembly of the macrocyclic domain, and, in the case of zampanolide, a Curtius rearrangement/acylation tactic to install the N-acyl hemiaminal. The complete relative and absolute stereochemistries for both (+)-zampanolide and (+)-dactylolide were also assigned, albeit tentatively in the case of (+)-zampanolide (1).
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