Synthesis And Antimicrobial Activities Of 3-CH₂COOCH₃/-CH₂COONa Substituted 1, 5-benzothiazepines

1,5-benzothiazepine is a kind of compound which has important physiological activities. Some of its derivatives have been used in clinic as antianxiety drugs,hyprosis and cardiovascular medicines.Therefore,its syntheses,structures and pharmacological activities have been attracted wide attentions.At present,a variety of 2-and 4-substituted 1,5-benzothiazepines have been synthesized. However,it is almost no reported about the 3-substituted 1,5-benzothiazepines.Our team has conducted relatively further research on this area.Some special structure of the compounds, such as 2 or 4-substituted 1,5-benzothiazepines by ester,have remarkable antimicrobial aetivities,expecially higher antifungal activities.As a continuation of our studies,a series of 3-CH₂COOCH₃ substituted 1,5-benzothiazepines are synthesized.On this basis,we continue to hydrolyze ester to its salt and we get 18 novel 3-CH₂COOCH₃/-CH₂COONa 1,5-benzothiazepines which haven't been reported yet.The structure of these compounds is determined by IR,¹H NMR,MS and Elementary Analysis.Reaction mechanism of this reaction is also discussed and their antibacterial activities have been researched.The work indicates that some special feature and the novel physiological activity will be an important significance to their antibacterial activities.And all of the works in this area is reported for the frist time.The main jobs in this thesis is as follows:Fristly,a series of novel 3-CH₂COOCH₃/-CH₂COONa 1,5-benzothiazepine is synthesized by some steps where different substituted benzene is used for raw materials,and its structures are determined by IR,¹H NMR,MS and Elementary Analysis.The procedure contains Friedel-Crafts reaction,Esterification reaction,Mannich reaction,Cycloaddition reaction and Hydrolysis.The mechanism of these reactions is also discussed.Secondly,in order to get a better result,reaction conditions are optimized,especially for the process which has an important influence on the technology.As a result,the operation is easier,the yield and purity is better than before.Thirdly,antibacterial activities of these novel compounds have been researched in vitro. The results show that:3-CH₂COOCH₃/-CH₂COONa 1,5-benzothiazepine have perfect inhibition to the Candida.albicans,but not well to the Staphylococcus.aureus and Staphylococcus.epidermidis,and it is no inhibition to the Escherichia.coli.