Ionic liquid-catalyzed and microwave-assisted syntheses of pyrrolizine- and indolizinedione derivatives

Abstract

3H-Pyrrolo[2,1-a]isoindole-2,5-diones and isoindolo[2,1-a]quinoline-5,11-diones were synthesized by intramolecular cyclization of N-[2-oxo-3-(triphenyl-λ 5 -phosphanylidene)propyl]-and N-[2-(triphenyl-λ 5 -phosphanylidene)acetyl]phthalimides, respectively, in the presence of ionic liquid ([bmim][BF 4 ], 10 mol %) as catalyst or under microwave irradiation. R = H (a), Me (b), MeOC(O) (c).Pyrrolizidine and indolizidine alkaloids constitute a class of pharmacologically important compounds [1-3] isolated from natural sources. Pyrrolizidine-and indolizidinedione derivatives have found versatile applications in medicine, primarily as CNS stimulators and antidiabetic, antiviral, antimicrobial, and antitumor drugs [4][5][6][7]. Recent studies have shown that natural alkaloids of the pyrrolizidine and indolizidine series (mappicine and mappicine ketone) exhibit high antiretroviral activity, so that they can be used as efficient drugs in a new line of AIDS chemotherapy [8]. Increased interest in pyrrolizidine-and indolizidinedione derivatives stimulates search for and development of new simple, inexpensive, and general methods for their preparation.We previously showed [9-13] that keto-stabilized sulfonium and phosphonium ylides derived from N-substituted α-and β-amino acids undergo intramolecular cyclization. We synthesized compounds having pyrrolizine and indolizine fragments from phosphorus ylides I and II which were obtained by acylation of simple alkylidenephosphoranes with N-phthaloyl amino acids III and IV (transylidation), which allowed us to considerably reduce the number of