Study On The Synthesis Of 1,2,3-Triazole Substituted β-Lactams Derivatives And Their Biological Activities

Many compounds containing the 1,2,3-triazole ring orβ-lactam ring have potent cytotoxic activity and other biological activities. They have found widespread use in combinatorial and medicinal chemistry. As recently been reported, the 1,2,3-triazole substitutedβ-lactam compounds have a wide variety of biologically active. The studies on the synthesis and bioassay of these compounds are important for finding biologically potent novel functional entities.Encouraged by recent studies of 1,2,3-triazole andβ-lactam compounds, a series of 1,2,3-triazole substitutedβ-lactam compounds were synthesized using active groups splicing method of active functional group 1,2,3-triazole introduced into 4-acetoxyβ-lactam and the biological activities of these compounds were also evaluated. The results and details are shown below:1. In this dissertation,31 novel 1,2,3-triazole substituted P-lactam compounds were synthesized. CompoundsⅡ-4a were synthesized via copper-catalyzed three-component click reaction of 4-acetoxyβ-lactam, sodium azide and alkynes. Their derived compoundsⅡ-4b were synthesized via deprotection of t-butyldimethylsilyl. The structures were characterized by NMR, IR and MS.2. The preliminary bioassay test indicated that some of them exhibited a certain antitumor activity to U87mG and HepG2 cells in vitro by MTT assay. Compounds II-4al2 exhibited greatest potency aganist U87mG cells with IC50 values of 2.94μg/mL, was more active than DDP and CPT-11. Compounds II-4bl3 exhibited greatest potency aganist HepG2 cells with IC50 values of 9.18μg/mL, was more active than CPT-11. In addition, compounds containing t-butyldimethylsilyl protection group were more active than their counterparts. Meanwhile, the morphology of HepG2 cells apoptosis was observed.The research work of this dissertation laid the foundation for the further studies of structure-activity relationship of 1,2,3-triazole substitutedβ-lactam compounds and the development of efficiency and low toxicity of lead compounds.