Multicomponent/Palladium-Catalyzed Cascade Entry to Benzopyrrolizidine Derivatives: Synthesis and Antioxidant Evaluation
2015-11-06T00:00:00Z (GMT) by
A versatile and efficient protocol for the synthesis of highly substituted benzopyrrolizidines (tetrahydro-3<i>H</i>-pyrrolo[2,1-<i>a</i>]isoindol-3-ones) is reported. The strategy consisted of an Ugi four-component reaction/elimination methodology to afford dehydroalanines containing <i>trans-</i>cinnamic acid derivatives and different substituted 2-bromobenzylamines, followed by a palladium-catalyzed 5-exo-trig/5-exo-trig cascade carbocyclization process. Gratifyingly, benzopyrrolizidines were obtained in moderate to good yields (42–77%) with a <i>Z</i> geometry due to the structural requirements for <i>syn</i>-β-hydride elimination. The prepared heterocyclic scaffolds are decorated with several substituents and incorporate a benzopyrrolizidine-fused system, along with an embedded cinnamic acid derivative, two privileged medicinal chemistry scaffolds. Additionally, since some of the compounds are derived from the well-known antioxidants ferulic and sinapinic acids, they were tested for their in vitro antioxidant capacity. The data suggested that compounds having a <i>p-</i>hydroxyl group showed moderate 2,2-diphenyl-1-picrylhydrazyl-radical-scavenging activity and were effective antioxidants in preventing lipoperoxidation in a thiobarbituric acid reactive substances assay.