RESUMO
Two new guaianolides, named chinensiolides D (5) and E (6), were isolated from Ixeris chinensis Nakai, and their structures were determined to be 10alpha-hydroxy-3-oxoguaia-11(13)-eno-12,6alpha-lactone (5) and 10alpha-hydroxy-3beta-O-[2,6-di(p-hydroxyphenylacetyl)-beta-glucopylanosyl]guaia-4(15),11(13)-dieno-12,6alpha-lactone (6). The first isolation of (11S)-10alpha-hydroxy-3-oxoguaia-4-eno-12,6alpha-lactone (4) from natural sources and its characterization are also reported. Chinenciolide E (6) showed significant growth inhibitory activity toward VA-13 malignant lung tumor cells (IC50 = 0.72 microM).
Assuntos
Antineoplásicos Fitogênicos , Asteraceae/química , Medicamentos de Ervas Chinesas , Plantas Medicinais/química , Sesquiterpenos de Guaiano , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Concentração Inibidora 50 , Molécula 1 de Adesão Intercelular/biossíntese , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Estrutura Molecular , Sesquiterpenos de Guaiano/química , Sesquiterpenos de Guaiano/isolamento & purificação , Sesquiterpenos de Guaiano/farmacologia , Células Tumorais CultivadasRESUMO
Methodology for synthesis of exo-endo cross-conjugated dienones with trans- and cis-decalin systems has been reported. Bromination of the silyl enol ether of alpha'-methyl alpha,beta-unsaturated ketones with PTAB and successive dehydrobromination of the resulting alpha'-bromo-alpha'-methyl alpha,beta-unsaturated ketones under three conditions (DBU/PhH; TBAF/THF; Li(2)CO(3), LiBr/DMF) gave the desired exo-endo cross-conjugated dienones in good yield. This method was applied to the syntheses of dehydrobrachylaenolide (1), isodehydrochamaecynone (5c), and trans-isodehydrochamaecynone (11) starting from tuberiferine (7), chamaecynone (5a), and trans-chamaecynone (9). Eudesmanolides possessing an alpha-methylene gamma-lactone moiety, i.e., 1, 7, and 13, exhibited significant inhibitory activity toward the induction of the intercellular adhesion molecule-1 (ICAM-1). Compound 1 showed greater activity than 7 and 13. All compounds possessing an ethynyl group, 5d, 9, 11, and 14, showed the same degree of termiticidal activity, and the exo-endo cross-conjugated dienone structure in 11 had no influence on the activity.
