Synthesis And Antibacterial Activity Of 1,5-benzodiazepine Lactone Compounds

Benzodiazepines and their polycyclic derivatives are a very important class of bioactive compounds. They are finding numerous new applications and are widely used as anticonvulsant, anti-inflammatory, analgesic, hypnotic, sedative, and antidepressive agents.It has high application value and research prospects. In recent years, some 1,5-benzodiazepines with high antibacterial activity were found. Moreover, some researches have reported that some compounds with lactone showed high biological activity, such as anti-feeding, anti-diabetic, especially anti-bacterial and anti-fungal. In order to obtained more 1,5-benzodiazepine derivatives with excellent antimicrobial activity, we designed and synthesized a novel series 1,5-benzodiazepine lactone compounds, investigated their antibacterial activity and structure-activity relationship. The following is the main content of the thesis:1.Synthesis of 2-phenyl-8-substituted 1,5-benzodiazepines with propiolactone in 4.Firstly, middle compounds III were synthesized where ethyl acetoacetate and substituted benzaldehyde are the starting material.The reaction was conducted in the green solvent Et OH in the presence of Na OH by reflux.The target compounds II were got from the reaction between the middle compounds and o-phenylenediamine through nucleophilic addition, cyclization and esterification. The structures of all the products were characterised by 1H NMR, IR, MS, elemental analysis and X-ray single-crystal diffraction. The possible reaction mechanism is proposed.2.Synthesis and antibacterial activity of 2-phenyl-4-methyl-8-substituted 1,5-benzodiazepines-3,4-butyrolactone: Firstly, middle compounds III were synthesized where ethyl levulinatee and substituted benzaldehyde are the starting material.The reaction was conducted in the green solvent Et OH in the presence of Na OH at ice-bath.The target compounds IV were got from the reaction between the middle compounds and o-phenylenediamine through nucleophilic addition, cyclization and esterification. In addition,all the synthesized compounds have been evaluated for their antimicrobial activities. The results of bioactive assay showed that most of the tested compounds displayed execelent effects on the growth of the tested microorganisms. All the active compounds showed better antibacterial activity than antifungal activity. The inhibition zone diameter of compound IVah against S. aureus was 29.70 mm, and the inhibition zone diameter of compound IVo against E. coli was 31.70 mm. The value of MIC were found more poten than Ciprofloxacin about IVo and against S. aureus. So compound IVo can be considered lead compounds for drug development.3. The relationship between structures and antibacterial activities of compounds IV was discussed by DFT method on B3LYP/ 6-31 G level. That can obtain the datas about bond lengths, bond angles, Mulliken charge, HOMO, LUMO and orbital contribution of the compounds. These are necessary to the study of structure-activity relationship of the compounds IV. That can obtain the datas about the relevant structural parameters and frontier molecular orbital energy data.