title: Total synthesis of the originally proposed and revised structures of palmerolide A and isomers thereof.
abstract: Palmerolide A is a recently disclosed marine natural product possessing striking biological properties, including potent and selective activity against the melanoma cancer cell line UACC-62. The total syntheses of five palmerolide A stereoisomers, including the originally proposed (1) and the revised [ent-(19-epi-20-epi-1)] structures, have been accomplished. The highly convergent and flexible strategy developed for these syntheses involved the construction of key building blocks 2, 19-epi-2, 20-epi-2, ent-2, 3, ent-3, 4, and ent-4, and their assembly and elaboration to the target compounds. For the union of the building blocks, the Stille coupling reaction, Yamaguchi esterification, Horner-Wadsworth-Emmons olefination, and ring-closing metathesis reaction were employed, the latter being crucial for the stereoselective formation of the macrocycle of the palmerolide structure. The Horner-Wadsworth-Emmons olefination and the Yamaguchi lactonization were also investigated and found successful as a means to construct the palmerolide macrocycle. The syntheses were completed by attachment of the enamide moiety through a copper-catalyzed coupling process.
authors.affiliation: Chemical Synthesis Laboratory@Biopolis, Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research, 11 Biopolis Way, The Helios Block, #03-08, Singapore 138667. kcn@scripps.edu
authors.forename: K C
authors.initials: KC
authors.lastname: Nicolaou
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Sun
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Guduru
authors.forename: Biswadip
authors.initials: B
authors.lastname: Banerji
authors.forename: David Y-K
authors.initials: DY
authors.lastname: Chen
mesh_terms: D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: D018942:Macrolides; C522534:palmerolide A