RESUMEN
Multi-birds with one stone: A cascade coupling strategy was developed for the synthesis of ß-carbolines. The method can direct the synthesis of ß-carboline and isoquinoline-containing natural products with high yields. Moreover, this protocol can also be further applied towards the total synthesis of natural products fascaplysin and papaverin (see scheme).
Asunto(s)
Productos Biológicos/síntesis química , Carbolinas/síntesis química , Isoquinolinas/síntesis química , Productos Biológicos/química , Carbolinas/química , Indoles/síntesis química , Indoles/química , Isoquinolinas/química , Estructura Molecular , Papaverina/síntesis química , Papaverina/químicaRESUMEN
The concise synthesis of 3-substituted or non-C3-substituted isoquinolines through Rh-catalyzed sequential oxidative C-H activation/annulation with geminal-substituted vinyl acetates was developed with good functional group tolerance. The protocol was successfully applied to the total synthesis of the natural product papaverine.
Asunto(s)
Acetatos/química , Papaverina/síntesis química , Compuestos de Vinilo/química , Catálisis , Ciclización , Estructura Molecular , Oxidación-Reducción , Oximas/química , RodioRESUMEN
In an effort to increase the specificity of the potent phosphodiesterase inhibitor papaverine, we synthesized two series of novel 1-(4-aminobenzyl)- and 1-(4-aminophenyl)isoquinoline derivatives, incorporating alkylating moieties on the amine substituents. These compounds were evaluated for their inhibitory action on phosphodiesterase preparations from bovine heart and rat cerebral cortex. Studies were also conducted to determine whether these compounds were reacting with the enzymes in an irreversible manner. The compounds were potent inhibitors of the phosphodiesterases; however, no evidence was found for an irreversible inhibition.
Asunto(s)
3',5'-AMP Cíclico Fosfodiesterasas/antagonistas & inhibidores , 3',5'-GMP Cíclico Fosfodiesterasas/antagonistas & inhibidores , Corteza Cerebral/enzimología , Papaverina/análogos & derivados , Animales , Femenino , Indicadores y Reactivos , Papaverina/síntesis química , Papaverina/farmacología , Ratas , Ratas Endogámicas , Relación Estructura-ActividadRESUMEN
6,7-Dimethoxyphthalazine was obtained in four steps from veratric acid and converted to its Reissert compound. Alkylation of this Reissert compound with 3,4-dimethoxybenzyl chloride followed by hydrolysis gave 3-azapapaverine.
Asunto(s)
Papaverina/análogos & derivados , Ftalazinas , Piridazinas , Papaverina/síntesis químicaRESUMEN
Two enantiomeric pairs of neuromuscular junction blocking agents were prepared in which an asymmetric carbon atom is adjacent to an asymmetric quaternized nitrogen moiety. The blocking agents were obtained from the enantiomers of laudanosine by stereoselective quaternization with benzyl and ethyl iodides. Curarimimetic potencies were measured with an in vivo cat hypoglossal nerve-tongue muscle preparation. The studies suggest that the asymmetry present in these structures does not lead to significant differences in blocking potency between enantiomers.
Asunto(s)
Fármacos Neuromusculares no Despolarizantes , Compuestos de Amonio Cuaternario/farmacología , Animales , Gatos , Técnicas In Vitro , Fármacos Neuromusculares no Despolarizantes/síntesis química , Papaverina/análogos & derivados , Papaverina/síntesis química , Papaverina/farmacología , Compuestos de Amonio Cuaternario/síntesis química , Estereoisomerismo , Relación Estructura-ActividadAsunto(s)
Isoquinolinas/síntesis química , Papaverina/síntesis química , Vasodilatadores/síntesis química , Animales , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Circulación Coronaria/efectos de los fármacos , Perros , Relación Dosis-Respuesta a Droga , Frecuencia Cardíaca/efectos de los fármacos , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Isoquinolinas/administración & dosificación , Isoquinolinas/farmacología , Cetonas/síntesis química , Cetonas/farmacología , Contracción Muscular/efectos de los fármacos , Papaverina/administración & dosificación , Papaverina/farmacología , Espectrofotometría Ultravioleta , Resistencia Vascular/efectos de los fármacos , Vasodilatadores/administración & dosificación , Vasodilatadores/farmacologíaRESUMEN
Stereoselective total synthesis of biologically active styryllactones 7-epi-goniofufurone, goniofufurone, goniopypyrone, goniotriol, altholactone, and etharvensin was achieved in high overall yields from a common intermediate derived from d-(-)-tartaric acid. It is based on the utility of a masked tetrol, comprising an alkene tether and four contiguous hydroxy groups. The pivotal reaction sequence involves hydroxy-directed lactonization via the oxidation of alkene, and subsequent elaboration to styryllactones. The masked tetrol was prepared by the extension of gamma-phenyl-gamma-hydroxy butyramide, readily obtained from the bis-dimethylamide of tartaric acid, employing a combination of selective Grignard additions and a stereoselective reduction.
Asunto(s)
Furanos/síntesis química , Lactonas/síntesis química , Papaverina/análogos & derivados , Pironas/síntesis química , Estirenos/síntesis química , Furanos/química , Lactonas/química , Estructura Molecular , Papaverina/síntesis química , Papaverina/química , Pironas/química , Estereoisomerismo , Estirenos/químicaRESUMEN
In 1915 Gadamer published in this journal [1] a procedure for the synthesis of papaverinol 2 from papaverine 1 in excellent yield. However, he did not investigate the formation of a violet fluorescence produced upon crystallization of papaverinol 2 from ethanol. The compound responsible for this fluorescence was isolated and identified as the yet unknown quaternary ammonium ion 4, a 6a, 12a-diazadibenzo-[a, g]fluorenylium derivative. The isolation of 4 and its structure determination by spectroscopic methods are described. However, its formation mechanism is unknown.
Asunto(s)
Papaverina/análogos & derivados , Papaverina/síntesis química , Colorantes Fluorescentes , Indicadores y Reactivos , Espectrometría de Masas , Compuestos de Mercurio/química , Oxidación-Reducción , Espectrometría de Fluorescencia , Espectrofotometría UltravioletaRESUMEN
Revised structure 8 is proposed for the quaternary bisbenzylisoquinoline alkaloid phaeantharine, based on spectrometric data. Phaeantharine, which occurs in Phaeanthus ebracteolatus (fam. Anonaceae), has current interest as a potential insecticide. Phaeantharine also exhibits moderate activity against gram-positive bacteria.
Asunto(s)
Alcaloides , Alcaloides/farmacología , Antibacterianos , Antiinfecciosos , Bacterias/efectos de los fármacos , Fenómenos Químicos , Química , Cromatografía en Capa Delgada , Hongos/efectos de los fármacos , Insecticidas , Espectroscopía de Resonancia Magnética , Papaverina/análogos & derivados , Papaverina/síntesis química , Papaverina/farmacología , PlantasRESUMEN
A new series of N-substituted bis-(tetrahydropapaverine) ring systems have been synthesised in expectation of better antispasmodic activity in comparison with papaverine. The synthesis of the targeted heterocycles is described along with a discussion of their structure activity relationship. The general synthetic methods of bis-(tetrahydropapaverine) analogues involve tetrahydropapaverine, various piperazines, diisocyanates and diisothiocyanates as starting materials. Pharmacological evaluation involves the in vitro antispasmodic activity on a freshly removed guinea pig ileum using a force displacement transducer amplifier connected to a physiograph. Among the analogues synthesized in the present study, N,N'-bis-[2-carbamoyl-1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolinyl]piperazine (22), was found to be the most potent muscle relaxant (IC(50): 0.31 microM).