Synthesis And Antitumor Activity Of Indolizines And Analogues

Indolizine has ten peripheralÏ€electrons and is isoelectronic with indole.It is also named pyrrolo[1,2-α]pyridine.Indolizine derivatives have a diversity of biological activity,such as antitumour,antiinflammatory,and antimicrobial activities. Pyrrolo[2,1-b]thiazole and pyrrolo[1,2-a]imidazole are components of various biologically active substances,which also contain N-fused pyrrole unit.In this thesis,the synthesis and antitumor activity of indolizines and their analogues were studied.1.Indolizines were synthesized by one pot reactions of pyridinium ylide with alkene in the presence of the mild oxidant TPCD.These reactions consisted of a 1,3-dipolar cycloaddition of N-ylides to alkenes,followed by an aromatization.Regioselective of 1,3-dipolar cycloaddition reaction was studied.Antiproliferative activity against Hep-G2 cell lines was tested and 5-fluorouracil was used as reference.Structure-activity relationship(SAR) was explored.2.Pyrrolo[2,1-b]thiazole and pyrrolo[1,2-a]imidazole were synthesized by the reactions of the corresponding N-ylides and electron-deficient alkenes in the presence of the base Et₃N and oxidant TPCD via 1,3-dipolar cycloaddition.The antitumor activity of some compounds was examined.Totally thirty-seven compounds were synthesized and characterized by FTIR,¹H and ¹³C NMR,MS and EA.And thirty-six compounds of them were not reported before.The study of biological activity showed that some of the newly synthesized compounds displayed potent-anfiproliferative activity against Hep-G2 cell lines.