Abstract
•A new series of spiropyrrolizidine derivatives was synthesized.•Structures of the synthesized compounds 4–6 were established by NMR spectroscopic and elemental analyses.•Theoretical calculations of compounds 4–5 were performed by DFT method with the methanol solvent.•All compounds were evaluated in vitro to their antimicrobial and anticoagulant activity.•D The structure-activity relationship (SAR) was discussed based on the molecular docking analysis.
The three-component cascade reaction of (E)-3-arylidene-1-methyl-pyrrolidine-2,5-diones, L-proline and isatin have been well established. It forms a new series of spiropyrrolizidine derivatives with wide structural complexity and diversity through an unprecedented isomerization with moderate to excellent yield. Spiro adducts were formatted by treatment of the dipolarophiles with in situ generated azomethine ylides from L-proline and isatin. In addition, these cycloadducts underwent retro 1,3-dipolar cycloaddition yielding unexpected regioisomers. The structures of obtained spiro[pyrrolizidin-2,3-oxindoles] 4–6 were elucidated by NMR spectroscopic and elemental analyses. Further, it was simulated through theoretical calculation in methanol at DFT-B3LYP/6–31G* level of theory. The synthetized compounds were then evaluated in vitro to study their antimicrobial activity against different species of bacteria and fungi as well as their anticoagulant activity. The antimicrobial and anticoagulant activities of our oxindoles show moderate to strong activity as compared to standard drugs. The structure-activity relationship (SAR) is discussed based on the molecular docking analysis.