RESUMEN

Sesquiterpene lactones are known to be active, but are also known to present high cytotoxicity. In the present work an evaluation of how slight structural alterations affect the cytotoxicity and the schistosomicidal activity of sesquiterpene lactones was undertaken. More specifically, we assessed the activity of budlein-A, a furanoheliangolide sesquiterpene lactone, and four of its derivatives. The structural modifications of budlein-A, presented in this work, diminished the cytotoxicity and changed the antiparasitary behavior of the molecule. They also provided data for a better understanding of the sesquiterpene lactone cytotoxicity. The establishment of the structures of three synthesized sesquiterpene lactones on the basis of NMR and HRESIMS data is also presented here. Complete and detailed (1)H and (13)C 1D and 2D NMR data, with measurements of all J values and all multiplicities clarified, are presented for five sesquiterpene lactones for the first time.

Asunto(s)

Antiparasitarios/farmacología , Productos Biológicos/farmacología , Lactonas/farmacología , Schistosoma mansoni/efectos de los fármacos , Esquistosomicidas/farmacología , Sesquiterpenos/farmacología , Animales , Antiparasitarios/síntesis química , Antiparasitarios/química , Productos Biológicos/síntesis química , Productos Biológicos/química , Biomphalaria , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Lactonas/síntesis química , Lactonas/química , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Pruebas de Sensibilidad Parasitaria , Esquistosomicidas/síntesis química , Esquistosomicidas/química , Sesquiterpenos/síntesis química , Sesquiterpenos/química , Relación Estructura-Actividad

RESUMEN

A series of 3(2H)-furanones, based on side-chain modifications of a parent 3(2H)-furanone, was synthesized in good yield. The parent compound was prepared by hydrogenolysis, and subsequent acid hydrolysis, of isoxazole derivatives. The isoxazole was prepared by a [3+2] 1,3-dipolar cycloaddition reaction between 3-butyn-2-ol and nitrile oxide.

Asunto(s)

Furanos/química , Alquilación , Alquinos/química , Butanoles/química , Reacción de Cicloadición , Furanos/síntesis química , Nitrilos/química

RESUMEN

The solvent has a significant influence in the rate of reactions promoted by Stryker's reagent. The reactions performed in THF were, in most cases, faster than in toluene.

Asunto(s)

Furanos/química , Tolueno/química , Hidrocarburos Aromáticos con Puentes/síntesis química , Hidrocarburos Aromáticos con Puentes/química , Furanos/síntesis química , Conformación Molecular , Sesterterpenos , Solventes/química , Estereoisomerismo

RESUMEN

The herbivory activity of the bordered patch larvae (Chlosyne lacinia, Lepidoptera) on leaves of a Brazilian population of Tithonia diversifolia and the antifeedant potential of its leaf rinse extract were investigated. The caterpillars fed only on the adaxial face, where the density of glandular trichomes is very low, and avoided the abaxial face, which contains high levels of trichomes. Deterrent activity against the larvae was observed in leaf discs treated with leaf rinse extract at concentrations of 1-5% of fresh leaf weight. High-performance liquid chromatography (HPLC) analysis indicated that sesquiterpene lactones are the main constituents of the glandular trichomes. Dichloromethane rinse extracts of the leaves and inflorescences were chemically investigated, and 16 compounds were isolated and identified: 14 sesquiterpene lactones, a flavonoid and a diterpenoid. In this study, five sesquiterpene lactones are described for the first time in the genus, including two lactones, one of which has an unusual seco-guaianolide skeleton. Our findings indicate that the caterpillars avoid the sesquiterpene-lactone-rich glandular trichomes, and provide evidence for the antifeedant activity of the dichloromethane leaf rinse extract. In addition, a study of the seasonal variation of the main constituents from the leaf surface throughout a year demonstrated that a very low qualitative but a very high quantitative variation occurs. The highest level of the main metabolite tagitinin C was observed between September and October and the lowest was from March to June, the later corresponding to the period of highest infestation by the larvae.

Asunto(s)

Asteraceae/química , Insectos/efectos de los fármacos , Insectos/fisiología , Extractos Vegetales/farmacología , Animales , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Larva/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Extractos Vegetales/química , Hojas de la Planta/química , Estaciones del Año

RESUMEN

A complete NMR analysis with full assignment for (1)H and (13)C NMR spectral data for 5-(acetyloxy)-3-hydroxy-9,10-dimethoxy-6-oxo-11-oxatricyclo[6.2.1.0(2,7)]undec-2-yl acetate is described. This compound was prepared by rapid hydrogenation of the unstable Diels-Alder adduct obtained from the reaction between 3,4-dimethoxyfuran and 2,5-diacetoxy-1,4-benzoquinone. Full homonuclear hydrogen coupling constants measurements and molecular mechanics calculations were performed for the determination of the relative stereochemistry.

Asunto(s)

Compuestos Heterocíclicos con 3 Anillos/química , Espectroscopía de Resonancia Magnética/métodos , Algoritmos , Isótopos de Carbono/química , Hidrógeno/química , Solventes/química , Estereoisomerismo , Volatilización

RESUMEN

A detailed analysis with total assignment of (1)H and (13)C NMR spectral data for a cycloheptenone derivative, a key intermediate for the synthesis of perhydroazulene terpenoids, is related. These assignments are based on 1D (1)H and (13)C NMR and on 2D NMR techniques including gCOSY, gHSQC, gHMBC, J-resolved and NOEDIF experiments. The unequivocal assignments were supported by theoretical chemical shifts and scalar coupling constant calculations at GIAO B3LYP/cc-pVDZ level from optimized structures at the same level of theory.

Asunto(s)

Cicloheptanos/química , Espectroscopía de Resonancia Magnética/métodos , Carbono/química , Isótopos de Carbono/química , Modelos Químicos , Modelos Moleculares , Conformación Molecular , Estructura Molecular , Protones

RESUMEN

Detailed assignments of (1)H and (13)C NMR spectral data for 13 beta-substituted cycloenones are reported. The assignments are based on 1D (1)H and (13)C NMR and on 2D shift-correlated ((1)H,(13)C-HMQC and HMBC), J-resolved and COSY and double irradiation experiments.

Asunto(s)

Cetonas/química , Espectroscopía de Resonancia Magnética/métodos , Isótopos de Carbono , Deuterio , Espectroscopía de Resonancia Magnética/normas , Estructura Molecular , Protones , Estándares de Referencia , Valores de Referencia

RESUMEN

We have found that some of the usually poor dienophiles (2-cycloenones) can undergo Diels-Alder reaction at -78 degrees C with unusually high stereoselectivity in the presence of niobium pentachloride as a Lewis acid catalyst. A remarkable difference in reaction rates for unsubstituted and alpha- or beta-methyl substituted 2-cycloenones was also observed.

RESUMEN

A simple and efficient method for the preparation of 1-methyl-3-oxo-7- oxabicyclo[2.2.1]hept-5-en-2-carboxylic acid methyl ester (1) is described. The first step is a highly regioselective Diels-Alder reaction between 2-methylfuran and methyl-3-bromo- propiolate. A remarkably difficult ketal hydrolysis reaction was effected by treatment with HCl, a simple reagent that was shown to be more efficient, in this case, than commonly used more elaborate methods.

Asunto(s)

Compuestos Bicíclicos Heterocíclicos con Puentes/síntesis química , Compuestos Bicíclicos con Puentes/química , Compuestos Bicíclicos con Puentes/síntesis química , Ácidos Carboxílicos/química , Ésteres/síntesis química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Catálisis , Ésteres/química , Hidrólisis , Estructura Molecular , Estereoisomerismo

RESUMEN

We describe a complete analysis of the 1H and 13C spectra of the anti-inflamatory, schistossomicidal and trypanosomicidal sesquiterpene lactone 15-deoxygoyazensolide. This lactone, with a structure similar to other important ones, was studied by NMR techniques such as COSY, HMQC, HMBC, Jres and NOE experiments. The comparison of the data with some computational results led to an unequivocal assignment of all hydrogen and carbon chemical shifts, even eliminating some previous ambiguities. We were able to determine all hydrogen coupling constants (J) and signal multiplicities and to confirm the stereochemistry. A new method for the determination of the relative position of the lactonization and the position of the ester group on a medium-sized ring by NMR was developed.

Asunto(s)

Compuestos Heterocíclicos con 3 Anillos/química , Concentración de Iones de Hidrógeno , Enlace de Hidrógeno , Espectroscopía de Resonancia Magnética , Conformación Molecular , Extractos Vegetales/química , Plantas/química

RESUMEN

In this paper we describe an efficient six-step synthesis of crocetin-dimethylester that could be further reduced to a "four-step" synthesis through the use of in situ procedures. The simplicity of the whole process, the ready availability of starting materials, and the high overall yield render this strategy a very attractive synthesis of this very important compound, which is the key intermediate for the synthesis of several carotenoids and other polyene natural products.