Use of phosphonyl carbanions in the synthesis of anti-inflammatory active phosphorus-containing fused heterocycles and relevance phosphonates.
The reaction of Horner-Emmons reactant carbanions with 2-acetyl-5-methyl furan 1 and 2-acetyl-5-bromothiophene 9 resulted in phosphorus-containing fused bicyclic 5,5-membered and 5,6-membered systems 5a-c and 12a-c, respectively, as major reaction products along with minor (∼20%) amounts of phosphorylated heterocycles 3a-c and 10a-c. Further treatment of bromo-substituted bicyclic systems 12a-c with the corresponding carbanion proceeded as a substitution of bromine for the residue of the Horner-Emmons reactant to afford compounds 13a-c bearing endo- and exocyclic phosphorus atoms. Reaction of diethyl vinylphosphonate with 5-methylfuran 1 and 5-bromothiophene 9 provided spirofuran 8 as a sole reaction product and (5H-thieno[3,2-d]oxaphosphinin-2-yl)vinylphosphonate 15, respectively. Among the products, at 50 mg/kg dose, 4 compounds showed notable anti-inflammatory activity without toxicity side-effect.
Abdou
Wafaa M
WM
Chemical Industries Division, National Research Centre, Elbohouth Street, D-12622, Dokki, Cairo, Egypt. wabdou@link.net
Kamel
Azza A
AA
Shaddy
Abeer A
AA
D000818:Animals; D000838:Anions; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002351:Carrageenan / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced; D005260:Female; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D011916:Rats, Inbred F344; D021241:Spectrometry, Mass, Electrospray Ionization
D000838:Anions; D000893:Anti-Inflammatory Agents; D006571:Heterocyclic Compounds; D063065:Organophosphonates; D002351:Carrageenan