title: Chloropupukeanolides C-E: cytotoxic pupukeanane chlorides with a spiroketal skeleton from Pestalotiopsis fici.
abstract: Chloropupukeanolides C-E (8-10), three highly functionalized secondary metabolites featuring a novel spiroketal skeleton derived from the chlorinated tricyclo-[4.3.1.0(3, 7)]-decane (pupukeanane) and the 2,6-dihydroxy-4-methylbenzoic acid moieties, were isolated from the scale-up fermentation extract of the plant endophytic fungus Pestalotiopsis fici. The constitutions of compounds 8-10 were elucidated primarily by NMR experiments. Their relative configurations were deduced by analogy to metabolites 4-6, which were previously isolated from the same fungus. The absolute configuration of 8 was assigned by X-ray crystallography and those of 9 and 10 by quantum-chemical CD calculations. Biogenetically, chloropupukeanolides C-E (8-10) are presumably derived from the same oxidation-induced Diels-Alder reaction pathway as compounds 1 and 4-7, via the putative biosynthetic precursors 2 and 3. The opposite configurations of the complete "Southern parts" of 8 and 9 suggests that this Diels-Alder reaction is stereochemically not very selective. Compounds 8-10 showed significant cytotoxicity against a small panel of human tumor cell lines and weak activities against the pathogens of tropical diseases.
authors.affiliation: Key Laboratory of Systematic Mycology & Lichenology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, P R China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.forename: Torsten
authors.initials: T
authors.lastname: Bruhn
authors.forename: Liangdong
authors.initials: L
authors.lastname: Guo
authors.forename: Daniel C G
authors.initials: DC
authors.lastname: Götz
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: August
authors.initials: A
authors.lastname: Stich
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Che
authors.forename: Gerhard
authors.initials: G
authors.lastname: Bringmann
mesh_terms: D000818:Animals; D028241:Camellia sinensis / Q000382:microbiology; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D021261:Parasitic Sensitivity Tests; D051381:Rats; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D013237:Stereoisomerism; D013098:Xylariales / Q000737:chemistry*
chemical_list: D012717:Sesquiterpenes; C556958:chloropupukeanolide C; C556959:chloropupukeanolide D; C556957:chloropupukeanolide E