Stereoselective One-Pot Synthesis of Spiro-Indenoquinoxaline-Pyrrolidine Hybrids: Structural Elucidation and Biological Evaluation

Abstract

A concise and stereoselective four-component, one-pot protocol has been developed for the synthesis of a new class of spiro-indenoquinoxaline-pyrrolidine hybrids with α-aroylideneketene dithioacetals via [3+2] cycloaddition. This previously unexplored approach delivers structurally complex spiro frameworks in up to 85% yield with excellent endo-selectivity under mild, atom-economic conditions. Spectral, single-crystal X-ray diffraction, and DFT analyses unambiguously confirmed the structures and formation of the synthesized compounds. Among the library, compound 6g as an endo product exhibited the most useful dual biological profile, displaying >98% inhibition against Streptococcus pyogenes MTCC 1927 and Pseudomonas aeruginosa MTCC 424 (MIC = 125 µg/mL), together with 32.8% DPPH radical-scavenging activity.Furthermore, molecular docking revealed strong binding affinity mediated by hydrogen bonding and π-π stacking interactions, and the experimental MIC data are consistent with the results for comparative isomers. This study highlights a sustainable and stereo-controlled synthetic route to bioactive spiro-heterocycles with significant potential.