RESUMO
Ball milling of aromatic, heteroaromatic, vinylic, and aliphatic esters with ethanol and calcium nitride afforded the corresponding primary amides in a transformation that was compatible with a variety of functional groups and maintained the integrity of a stereocenter α to carbonyl. This methodology was applied to α-amino esters and N-BOC dipeptide esters and also to the synthesis of rufinamide, an antiepileptic drug.
Assuntos
Amidas , Ésteres , DipeptídeosRESUMO
A Ce(IV)-catalyzed three-component reaction between chalcones, anilines and ß-ketoesters followed by a microwave-assisted thermal cyclization afforded 1,3-diaryl-1,2-dihydroacridin-9(10H)-ones. Their microwave irradiation in nitrobenzene, acting both as solvent and oxidant, afforded fully unsaturated 1,3-diarylacridin-9(10H)-ones, which combine acridin-9-(10H)one and m-terphenyl moieties. Overall, the route generates three C-C and one C-N bond and has the advantage of requiring a single chromatographic separation.
Assuntos
Acridinas/química , Substâncias Intercalantes/química , Compostos de Terfenil/química , Compostos de Anilina/química , Catálise , Chalconas/química , Ciclização , Ésteres/química , Estrutura MolecularRESUMO
The therapeutic use of the traditional drugs against epilepsy has been hindered by their toxicity and low selectivity. These limitations have stimulated the design and development of new generations of antiepileptic drugs. This review explores the molecular targets and synthesis of the antiepileptic drugs that have entered the market in the 21st century, with a focus on manufacturer synthesis.
Assuntos
Anticonvulsivantes , Epilepsia , Anticonvulsivantes/síntese química , Anticonvulsivantes/farmacologia , Anticonvulsivantes/química , Anticonvulsivantes/uso terapêutico , Humanos , Epilepsia/tratamento farmacológico , Animais , Estrutura MolecularRESUMO
One interesting aspect of antioxidant organic molecules is their use as probes for the detection and quantitation of biologically relevant reactive oxidant species (ROS). In this context, a small library of dihydroterphenyl derivatives has been synthesised and studied as fluorescent chemodosimeters for detecting reactive oxygen species and hypochlorite. The fluorescence quantum yields of these molecules are negligible, while the corresponding aromatized compounds formed upon oxidation show moderate to high native fluorescence, depending on their structures. The fluorescence signal is quickly developed in the presence of trace amounts of the probe and the analytes in acetonitrile media at room temperature, with good analytical figures. ROS detection in aqueous media required incubation at 37 °C in the presence of horseradish peroxidase, and was applied to glucose quantitation by coupling glucose oxidation by O2 to fluorescence detection of H2O2. The mild reaction conditions and sensitive fluorescent response lead us to propose dihydroterphenyls with an embedded anthranilate moiety as chemosensors/chemodosimeters for ROS detection.
RESUMO
The three-component reaction between alkyl- or arylamines, ß-ketoesters and chalcones in refluxing ethanol containing a catalytic amount of Ce(IV) ammonium nitrate allowed the construction of a large library of highly substituted dihydro- m-terphenyl derivatives containing ß-alkylamino- or ß-arylamino ester moieties. This process generates three new bonds and one ring and proceeds in high atom economy, having two molecules of water as the only side product. Another domino process, in which the original MCR was telescoped with a subsequent aza Michael/retro-aza Michael sequence, allowed the one-pot preparation of a library of compounds with a N-unsubstituted ß-aminoester fragment. Finally, to extend the structural diversity of these libraries, we also examined the aromatization of the central ring of our compounds in the presence of dichlorodicyanoquinone. This reaction sequence did not affect the integrity of a stereogenic center belonging to the amino component.