Synthesis Of 2, 3/2, 5-dihydro-1, 5-benzothiazepines And The Search Of Their Antimicrobial Activities

1,5-benzothiazepine is a kind of compound which has important physiological activities. Some of his derivatives have been used in clinic as antianxiety drug, hypnogenetic and cardiovascular medicine. Therefore, its synthesis, structures and pharmacological activities have attracted wide attentions. But reference suggests, in order to get antibacterial effect, high concentration is necessary. In order to choice better 1,5-benzothiazepine with antibacterial activities, we have designed and synthesized six 4-methyl-2-aryl-3-ethoxycarbonyl-7-chloro- 2,3-dihydro-1,5-benzothiazepine(imine) and two 4-methyl-2-aryl-3-ethoxycarbonyl-7-chloro- 2,5-dihydro-1,5-benzothiazepine(enamine). The structures of the productions were determined by IR, 1H NMR and elementary analysis. meanwhile, the productions were researched about their antibacterial activities. Base on the research of imine and enamine 1,5-benzothiazepine about antibacterial activities, we have researched on their connection of structure and effect. moreover, synthesization and abruption of imine and enamine were researched. a series of novel solubility 1,5-benzothiazepine have been researched about synthesization of condition.Main results:(1) 2-phenylmethylene ethyl acetoacetate were synthesized from benzaldehyde and ethyl acetoacetate by konevengel condensation reaction. we have researched and improved the conditions of separation and purification.(2) 2-(1-aryl-1-o-aminophenylthio methyl)-ethyl acetoacetate were synthesized from 2-amido-4-chlorothiophenol and 2-phenylmethylene ethyl acetoacetate, 1,5-benzothiazepine were synthesized from 2-(1-aryl-1-o-aminophenylthio methyl)-ethyl acetoacetate under the catalyze of acetic acid. The structures of the productions were determined by IR, 1H NMR and elementary analysis.(3) We have researched antibacterial activities of these compounds. It suggests that eight comopouds exhibited higher antibacterial activity against C. albicans, S. aureus, S. epidermidis than antibacterial activity against E. coli.â…¢a,â…¢f showed significant activity, and the others showed moderate activity. the imine of 1,5-benzothiazepine exhibited higer antibacterial activity against C. albicans, S. aureus, S. epidermidis than the enamine of 1,5-benzothiazepines'. These results indicated that the imine of 1,5-benzothiazepine structure (C=N) seems to play an important role in the antimicrobial activity.(4) We have researched the conditions of synthesization and separation about the imine and enamine of 1,5-benzothiazepine. We have brought forward that the imine of 1,5-benzothiazepine is the production of speed control and the enamine of 1,5-benzothiazepine is the production of balance control for the first time. We have found the condition of separation on the imine and enamine of 1,5-benzothiazepine.(5) We have researched a series of novel solubility 1,5-benzothiazepine about synthesization of condition. and we had achieved the synthesization of two steps.