RESUMEN
A series of l-pyroglutamic acid analogues from natural product lead were designed and synthesized, as well as their antifungal activities against Phytophthora infestans, neuritogenic activities, antibacterial activities and anti-inflammatory activities are described. The bioassays and SAR study showed that the majority of l-pyroglutamic acid esters have a significant antifungal activity against P. infestans, especially 2d and 2j demonstrated the best activities with EC50 values of 1.44 and 1.21⯵gâ¯mL-1, which were about seven times that of commercial azoxystrobin (7.85⯵gâ¯mL-1). Moreover, compounds 2e, 2g and 4d displayed anti-inflammatory activity against LPS-induced NO production in BV-2 microglial cells; neuritogenic activity in NGF-induced PC-12 cells is the same activity. This study demonstrates that compounds 2d and 2j are potential drugs to control P. infestans.
Asunto(s)
Antifúngicos/síntesis química , Productos Biológicos/química , Ácido Pirrolidona Carboxílico/análogos & derivados , Animales , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Línea Celular , Lipopolisacáridos/farmacología , Ratones , Microglía/citología , Microglía/efectos de los fármacos , Microglía/metabolismo , Óxido Nítrico/metabolismo , Células PC12 , Phytophthora infestans/efectos de los fármacos , Ácido Pirrolidona Carboxílico/síntesis química , Ácido Pirrolidona Carboxílico/farmacología , Ratas , Relación Estructura-ActividadRESUMEN
Asymmetric catalytic synthesis of 2,3-allenamides from hydrogen-bond-stabilized enynamides in the presence of quinine-based bifunctional squaramide organocatalysts is described. This protocol forms a variety of 2,3-allenamides in high yields and excellent stereoselectivities, in which the elaborated introduction of intramolecular H-bonds within the N, N-bidentate amide group constitutes one of the keys to this highly enantioselective transformation. The synthetic practicality of this reaction has been demonstrated by the axis-to-center chirality transfer of allenamides to furnish enantiomerically enriched building blocks.