Regiospecific synthesis and biological evaluation of spirooxindolopyrrolizidines via (3+2) cycloaddition of azomethine ylide.

摘要

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 mug/mL) whereas 4d against Candida albicans and 4b and 4d against Rhizopus sp. showed beneficial antifungal activity at minimum concentration.