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.

A 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 as PowerPoint slide