Total Syntheses of (+)-Zampanolide and (+)-Dactylolide Exploiting a Unified Strategy

The first total syntheses of (+)-zampanolide (<b>1</b>) and (+)-dactylolide (<b>2</b>), 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 <i>cis</i>-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 <i>N</i>-acyl hemiaminal. The complete relative and absolute stereochemistries for both (+)-zampanolide and (+)-dactylolide were also assigned, albeit tentatively in the case of (+)-zampanolide (<b>1</b>).