Regiospecific synthesis and biological evaluation of spirooxindolopyrrolizidines via [3+2] cycloaddition of azomethine ylide

Reaction of (E)-3-aryl-1-(thiophen-2-yl)prop-2-en-1-ones with azomethine ylide (generated in situ via decarboxylative condensation of isatin with l-proline) in refluxing methanol afforded 1′-(aryl)-2′-(2-thienylcarbonyl)-spiro[3H-indole-3,3′-[3H]pyrrolizin]-2-ones as the sole product in a regiospecific manner. The synthesized compounds have been characterized by their elemental, analytical and spectral studies. The synthesized compounds were screened for their antibacterial and antifungal activities against a spectrum of microbial organisms. These studies proved that compounds 1′-(p-chlorophenyl)-2′-(2-thienylcarbonyl)-spiro[3H-indole-3,3′-[3H]pyrrolizin]-2-one (4b), 1′-(p-fluorophenyl)-2′-(2-thienylcarbonyl)-spiro[3H-indole-3,3′-[3H]pyrrolizin]-2-one (4d) and 1′-(p-methoxyphenyl)-2′-(2-thienylcarbonyl)-spiro[3H-indole-3,3′-[3H]pyrrolizin]-2-one (4h) against Staphylococcus aureus, 1′-(p-chlorophenyl)-2′-(2-thienylcarbonyl)-spiro[3H-indole-3,3′-[3H]pyrrolizin]-2-one (4b), 1′-(p-methylphenyl)-2′-(2-thienylcarbonyl)-spiro[3H-indole-3,3′-[3H]pyrrolizin]-2-one (4c) and 1′-(p-fluorophenyl)-2′-(2-thienylcarbonyl)-spiro[3H-indole-3,3′-[3H]pyrrolizin]-2-one (4d) against Salmonella typhi show maximum inhibition potency at low concentration (6.25 μg/mL) whereas 4d against Candida albicans and 4b and 4d against Rhizopus sp. showed beneficial antifungal activity at minimum concentration.

Graphical abstractA series of spirooxindolopyrrolizidines prepared in good yields from the reaction of thiophenyl-substituted dipolarophiles, isatin and l-proline under reflux conditions show good in vitro antibacterial and antifungal activity.Figure optionsDownload full-size imageDownload as PowerPoint slide