The Research On Synthesis And Antimicrobial Activity Evaluation Of1,5-benzodiazepine And1,5-benzothiazepine Derivatives

1,5-benzodiazepines and1,5-benzothiazepines are a kind of seven-memberedheterocycle compounds and have both important physiological activities and biologicalactivities. Many derivatives of them are nowadays widely used as antianxiety, antidepressant,sedative, anticonvulsant and analgesic. Therefore the research of its unique chemical structureand special physiological activity has been getting people’s attention.According to the literature1,5-benzodiazepines have good antibacterial activity. Thestudy found that the substituents on the aromatic ring have a great impact on antibacterialactivity. Especially the introduction of halogen groups in the benzene ring can increase itsbiological activity;while the introduction of the ester can increase the body’s fat-soluble,thereby increasing its pharmacological activity. Therefore to get to the better activecompounds this paper has designed and synthesized twelve novel kinds of7-bromo-4-substituted phenyl-2,3-dihydro-1,5-benzodiazepine-2-methanoic acid ester and8-bromo-4-substituted phenyl-2,3-dihydro-1,5-benzodiazepine-2-methanoic acid esteraccording to principles of drug design and we have tested the antibacterial activities of thecompounds mentioned above.1,5-benzothiazepine has good biological and pharmacologicalactivity. According to the literature when sulfide oxidation into sulfone it will increase itsbiological activity. Therefore the paper has designed and synthesized five novel kinds of theoxidation products (sulfone) of2-alkoxyphenyl carbonyl-4-aryl-1,5–benzothiazepines and wehave tested the antibacterial activities of the compounds mentioned above.Besides we havedone the experimental study of the conditions on the synthesis reaction and get to the optimalreaction conditions of oxidation. We made a theoretical study on the the factors of affectingantibacterial activity of1,5–benzodiazepine compounds by the Gaussian03quantumchemistry package, density functional theory (DFT) at the B3LYP method, in the6-31G basisset level.This thesis includes the following parts:Firstly, twelve novel kinds of7-bromo-4-substituted phenyl-2,3-dihydro-1,5-benzodiazepine-2-methanoic acid ester and8-bromo-4-substitutedphenyl-2,3-dihydro-1,5-benzodiazepine-2-methanoic acid ester were synthesized where substituted benzene and maleic anhydride are the starting material after a three-step reactionand the structures of these new compounds are determined by IR、MS、1H NMR、elementalanalysis and13C NMR.Secondly, five novel kinds of the oxidation products (sulfone) of2-alkoxyphenylcarbonyl-4-aryl-1,5–benzothiazepines were synthesized where substituted benzene and maleicanhydride are the starting material after a four-step reaction and the structures of these newcompounds are determined by IR、MS、1H NMR、elemental analysis and13C NMR. Besideswe have done the experimental study of the conditions on the synthesis reaction and get to theoptimal reaction conditions of oxidation.Thirdly, antimicrobial activities of seventeen novel compounds are researched by filterpaper method. On the foundation of these results, the original structure-activity relationship isstudied.Lastly, We made a theoretical study on the the factors of affecting antibacterial activityof1,5–benzodiazepine compounds by the Gaussian03quantum chemistry package, densityfunctional theory (DFT) at the B3LYP method, in the6-31G basis set level.we found thatSeven-membered ring is the center of its biological activity and N atoms and C=N doublebond are the efficacy of the compound groups.