(2,4-cis and trans)-gigantecinone and 4-deoxygigantecin, bioactive nonadjacent bis-tetrahydrofuran annonaceous acetogenins, from Goniothalamus giganteus.
Two new acetogenins, (2,4-cis and trans)-gigantecinone (1), isolated as a mixture, and 4-deoxygigantecin (2), a known acetogenin whose absolute stereochemistry has not been determined previously, were isolated using activity-directed fractionation, from the bark of Goniothalamus giganteus. A key step in solving their absolute stereochemistries was the preparation of 1,4-diol formaldehyde acetal derivatives (1b and 2a). Using the advanced Mosher ester method and circular dichroism, the absolute stereochemistries of 1 and 2 were revealed and were found to be the same as that of gigantecin (3), which supports a common biogenetic origin. Both 1 and 1b showed potent and selective cytotoxicities against the PC-3 human prostate adenocarcinoma cell line. Against yellow fever mosquito larvae, 1 and 2 were more potent than rotenone in pesticidal activity. Longimicin C and a mixture of (2,4-cis and trans)-isoannonacin were also isolated for the first time from this species.
Alali
F Q
FQ
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Zhang
Y
Y
Rogers
L
L
McLaughlin
J L
JL
D000107:Acetylation; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000494:pharmacology; D009033:Culicidae; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D007306:Insecticides / Q000302:isolation & purification* / Q000633:toxicity; D007783:Lactones / Q000302:isolation & purification* / Q000494:pharmacology / Q000633:toxicity; D009682:Magnetic Resonance Spectroscopy; D019441:Plant Epidermis / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D014407:Tumor Cells, Cultured
C108757:4-deoxygigantecin; D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D007306:Insecticides; D007783:Lactones; C108758:gigantecinone