title: Total synthesis of plakortide E and biomimetic synthesis of plakortone B.
abstract: The total synthesis of plakortide E (1a) is reported. A novel palladium-catalyzed approach towards 1,2-dioxolanes as well as an alternative substrate-controlled route leading exclusively to cis-highly substituted 1,2-dioxolanes have been developed. A lipase-catalyzed kinetic resolution was employed to provide optically pure 1,2-dioxolane central cores. Coupling of the central cores and side chains was achieved by a modified Negishi reaction. All four isomeric structures of plakortide E methyl ester, namely, 26a-d were synthesized. One of the structures, 26d, was shown to be identical with the natural plakortide E methyl ester on the basis of (1)H, (13)C NMR spectra and specific rotation comparisons. With the plakortide E methyl ester (4S,6R,10R)-(-)-cis-26d and its other three isomers in hand, we successfully converted them into (3S,4S,6R,10R)-plakortone B (2a), and its isomers ent-2a, 2b and ent-2b via an intramolecular oxa-Michael addition/lactonization cascade reaction. Finally, saponification converted 1,2-dioxolane 26d into plakortide E (1a) whose absolute configuration (4S,6R,10R) was confirmed by comparison of spectral and physical data with those reported.
authors.affiliation: Department of Chemistry, Centre of Novel Functional Molecules, Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, PR China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Sun
authors.forename: Xiang-Yin
authors.initials: XY
authors.lastname: Tian
authors.forename: Zhen-Wu
authors.initials: ZW
authors.lastname: Li
authors.forename: Xiao-Shui
authors.initials: XS
authors.lastname: Peng
authors.forename: Henry N C
authors.initials: HN
authors.lastname: Wong
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D004146:Dioxanes / Q000138:chemical synthesis* / Q000737:chemistry; D004148:Dioxolanes / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D004146:Dioxanes; D004148:Dioxolanes; D007783:Lactones; C093753:plakortolide E; C517066:plakortone B; D010165:Palladium; D015107:4-Butyrolactone