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.
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India. thangabell2003@yahoo.co.in
Arumugam
A
Thangamani
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001391:Azo Compounds / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects; D003500:Cyclization; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D011759:Pyrrolidines / Q000737:chemistry* / Q000494:pharmacology; D012233:Rhizopus / Q000187:drug effects; D012485:Salmonella typhi / Q000187:drug effects; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013882:Thiosemicarbazones / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D001391:Azo Compounds; D011759:Pyrrolidines; D013141:Spiro Compounds; D013882:Thiosemicarbazones; C512188:azomethine