Synthesis Of Water-soluble 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 its derivatives have been used in clinic as antianxiety drug, hyprosis and cardiovascular medicine. Therefore, its syntheses, structures and pharmacological activities have been attracted wide attentions.A certain bioactive compound becomes a kind of drug which is related to their biological activity, but also to the various physical and chemical properties. Many bioactive compounds, since it haven’t the absorption, distribution, metabolism, elimination of such nature, and should not be applied in clinic. If a kind of drug has effective absorption and distribution in body, it should have a certain extent of fat-solubility and water-solubility. The drugs which is not only used in the oral administration , but also the injection or the infusion frequently, so the medicine is requested to be have a certain of water-solubility.However, the kind of 1,5-benzothiazepine which have antibacterial activity isn’t easy dissolved in water. Reference suggests, in order to getting antibacterial effect, high concentration is necessary. The kind of compound is hard to be practical medicine or its applications are limited without hydrophilic group’s modification.Our team has conducted relatively further research on the area. And some special structure of the compounds was remarkable antimicrobial activity and showed higher antifungal activity than antibacterial activity. The nature was first found and it has a better prospect. In this paper, a series of new ester-substituted 1,5-benzothiazepine is synthesized by some reaction steps. It is different substituted benzene in the system for raw materials. Seven novel 2-alkoxyl carbonyl-4-aryl-1,5-benzothiazepine which haven’t been reported. The structures of these productions are determined by IR、1HNMR、MS and elementary analysis. Reaction mechanism of this reaction was discussed. On this basis, the outcome continuing to hydrolyze, so a series of 4-aryl-1,5-benzothiazepine-2-sodium formate is synthesized and its structure is determined. We have researched antibacterial activities of these two series of 1,5-benzothiazepine. The work that founds special features and the new physiological activity will be an important significance. No current research reported in the literature.This thesis includes there major parts:1. In this paper, a series of new ester substituted 1,5-benzothiazepine was synthesized by some reaction steps that different substituted benzene is for raw materials, and is determined by IR、1HNMR、MS and elementary analysis. The synthesis procedure of a series of 2-alkoxyl carbonyl-4-aryl-1,5-benzothiazepine derivatives is maleic anhydride through Friede-Crafts reaction、esterification reaction and cycloaddition reaction. Mechanism of the reaction was discussed.2. We continue to use 2-alkoxyl carbonyl-4-aryl-1,5-benzothiazepine derivatives as raw material hydrolysis reaction and get a series of new water-soluble 4-aryl-1,5-benzothiazepine-2-sodium formate derivatives. We have done a detailed study and exploration on hydrolysis conditions、the isolation and purification methods. The piece of job founds for the synthesis of water-soluble 1,5-benzothiazepine.3. We have measured in vitro antibacterial activity of the two series compounds using filter paper method. Study results show that: the two series haven’t inhibition for the Escherichia.coli, have the better inhibition for the Staphylococcus.aureus and Staphylococcus.epidermidis, and have the best inhibition for the Candida.albicans.