Synthesis of multi-functionalized 1-azabicycles through MAOS acid catalyzed formal aza-[3+3] cycloaddition of heterocyclic enaminones with oxazolones

Abstract

This study describes the combination of microwave heating and green acid catalysis by Bi(NO3)3·5H2O and AcOH as a practical one-pot diastereoselective synthetic route to alkaloid-like multi-functionalized 3,4-disubstituted indolizidinones and quinolizidinones from cyclic enaminones and Erlenmeyer–Plöchl azalactone derivatives, as an alternative methodology to access these synthetically and biologically important classes of structural scaffolds in a simple way. The potential biological activity of some synthesized alkaloid-like derivatives was tested against the human tumor lineage hepatoma (HepG-2), and their inhibitory effect evaluated after 24 and 48 h. The indolizidine-like scaffold appears to be crucial to biological activity in the investigated compounds.