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.
Thangamani
Arumugam
A
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India. thangabell2003@yahoo.co.in
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