RESUMO
Free ortho-hydroxy cinnamate ester derivatives are evaluated in the synthesis of structurally diverse 4-aryl-coumarins via a tandem Heck-Matsuda cyclization reaction. Free phenolic groups were considered incompatible with such a reaction, which usually provide the corresponding diazo dyes. A concise and scalable route employing a ligand-free, Pd-catalyzed Heck-Matsuda arylation under aerobic conditions for the preparation of (R)-Tolterodine in high overall yield and ee is also presented.
Assuntos
Compostos Benzidrílicos/síntese química , Cinamatos/química , Cumarínicos/síntese química , Cresóis/síntese química , Fenilpropanolamina/síntese química , Compostos Benzidrílicos/química , Catálise , Cumarínicos/química , Cresóis/química , Ciclização , Ésteres , Estrutura Molecular , Paládio/química , Fenilpropanolamina/química , Estereoisomerismo , Tartarato de TolterodinaRESUMO
Toxicological and pharmacological studies demonstrated that the introduction of functional groups into the aromatic ring of diphenyl diselenide alter its effect. The aim of this study was to evaluate the in vitro effect of m-trifluoromethyl-diphenyl diselenide (m-CF(3)-C(6)H(4)Se)(2), p-chloro-diphenyl diselenide (p-Cl-C(6)H(4)Se)(2) and p-methoxyl-diphenyl diselenide (p-CH(3)O-C(6)H(4)Se)(2) on delta-aminolevulinate dehydratase (delta-ALA-D) and Na(+), K(+)-ATPase activities in rat brain homogenates. Diselenides inhibited delta-ALA-D activity (IC(50) 4-6 microM [concentration inhibiting 50%]), and dithiothreitol (DTT) restored the enzyme activity. ZnCl(2) (100 microM) did not restore delta-ALA-D inhibition caused by (p-Cl-C(6)H(4)Se)(2) and (m-CF(3)-C(6)H(4)Se)(2). Na(+), K(+)-ATPase activity was more sensitive to (p-Cl-C(6)H(4)Se)(2) and (m-CF(3)-C(6)H(4)Se)(2) (IC(50) 6 microM) than (p-CH(3)O-C(6)H(4)Se)(2) and (PhSe)(2) (IC(50) 45 and 31 microM, respectively). DTT restored the activity of Na(+), K(+)-ATPase inhibited by diselenides. The effect of diselenides on Na(+)/K(+)-ATPase is dependent on their substitutions in the aromatic ring. The mechanism through which diselenides inhibit delta-ALA-D and Na(+), K(+)-ATPase activities involves the oxidation of thiol groups.
Assuntos
Derivados de Benzeno/farmacologia , Encéfalo/enzimologia , Inibidores Enzimáticos/farmacologia , Compostos Organosselênicos/farmacologia , Sintase do Porfobilinogênio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , Animais , Derivados de Benzeno/química , Cloretos/farmacologia , Ditiotreitol/farmacologia , Técnicas In Vitro , Masculino , Compostos Organosselênicos/química , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Compostos de Zinco/farmacologiaRESUMO
The first total syntheses of four new polyacetylene compounds have been achieved using convergent routes, which involved Cadiot--Chodkiewicz copper-catalyzed cross-coupling reactions to sp-sp centers as the key steps. 19-Furan-2-ylnonadeca-5,7-diynoic acid (1), 19-furan-2-ylnonadeca-5,7-diynoic acid methyl ester (2), 2-pentacosa-7,9-diynylfuran (3), and 21-furan-2-ylhenicosa-14,16-diyn-1-ol (4) were stable and could be readily identified, isolated, and purified in high overall yields.
Assuntos
Produtos Biológicos/síntese química , Furanos/síntese química , Poli-Inos/síntese química , Produtos Biológicos/química , Catálise , Cobre/química , Furanos/química , Estrutura Molecular , Poli-Inos/químicaRESUMO
The aims of the present study were to investigate the possible involvement of glutamatergic system in seizures induced by diphenyl diselenide in rat pups (postnatal day, 12-14) and to evaluate the role of oxidative stress in seizures induced by diphenyl diselenide/glutamate. Glutamate (4 g/kg of body weight) administered in association with diphenyl diselenide (500 mg/kg of body weight) increased the latency for the appearance of the first seizure episode, reduced lipid peroxidation levels and catalase, Na+,K+-ATPase and delta-ALA-D activities. At the lowest dose (5 mg/kg of body weight), diphenyl diselenide reduced the appearance of seizure episodes induced by glutamate but did not alter the latency for the onset of the first episode. Glutamate uptake was inhibited in glutamate, diphenyl diselenide (the highest dose) and in the association of diphenyl diselenide (both doses) and glutamate groups. Pre-treatment with a N-methyl-D-aspartate (NMDA) receptor antagonist, MK-801 (5S,10R-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), significantly prolonged the latency for the onset for the first convulsive episode. A non-NMDA receptor antagonist, DNQX (6,7-dinitroquinoxaline-2,3-dione), did not protect seizures induced by diphenyl diselenide. The results of the present study demonstrated that: (a) when diphenyl diselenide and glutamate were administered concomitantly in pups, glutamate was the main responsible for the neurotoxic effects; (b) oxidative stress was not involved in glutamate-induced seizures; (c) NMDA glutamatergic receptors, were at least in part, involved in diphenyl diselenide- induced seizures; and (d) diphenyl diselenide, at the lowest dose, protected seizures induced by glutamate.