Total syntheses of (+)-zampanolide and (+)-dactylolide exploiting a unified strategy.
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).
Smith
Amos B
AB
Contribution 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
Safonov
Igor G
IG
Corbett
R Michael
RM
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis*; D018942:Macrolides / Q000138:chemical synthesis*; D008968:Molecular Conformation; D011161:Porifera / Q000737:chemistry; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007783:Lactones; D018942:Macrolides; C451487:dactylolide; C444900:zampanolide