Antimicrobial Activity And Structure-activity Relationship Of Fluoro-substituted-1,5-benzothiazepine

1,5-Benzothiazepine is a kind of heterocycle compound in clinical, which has importantphysiological activities. Some of its derivatives have been used in clinic as antianxiety drugs,hyprosis and cardiovascular medicines. Therefore, its syntheses, structures andpharmacological activities have been attracted wide attentions.For a long time, our laboratory has engaged in the investigation of the synthesis1,5-benzothiazepine derivatives and the research of their antimicrobial activities. A series ofderivatives of1,5-benzothiazepine have been synthesized, and after testing, some specialstructures of these compounds showed high antimicrobial activity, we called them leadcompounds. Based on the original2-ester substituted1,5-benzothiazepine and in accordancewith the principle of local modification of the drug synthesis, after changing the ester groupin the seven-membered, changing F-substituted position or the number on the benzene whichis in the seven-membered, the addition of Cl, replaceing the S,N,O or imine double bond, aseries of new type compounds had been synthesized. The synthesized compounds are testedfor and discussed about their antimicrobial, compared with lead compounds and investigatedfor the structure-activity relationships preliminarily. All of the study results will be importantfor screening for novel antifungal compounds.This thesis includes the following parts:Firstly, chalcone had been synthesized by the two methods. On the one hand, chalconehad been synthesized by the Friede-Crafts acylation, esterification reaction, wherefluorophenyl and maleic anhydride is used for the raw materials; On the other hand, differentF substituted acetophenone and glyoxylic acid as raw materials, had been synthesized forchalcone by aldol condensation, esterification, eliminate the reaction chalcone. All kinds ofchalcone had been target compounds by Michael addition reaction and intramoleculardehydration reaction. Furthermore, the structures of these new compounds are determined byIR, HRMS,1~H-NMR,13~C-NMR.Secondly, screening of antibacterial activities of newly synthesized compounds, wefound that some of the compounds especially of the fungus Cryptococcus neoformans has a good antibacterial activity. And its concentration gradient, the minimum inhibitoryconcentration (MIC), the minimum bactericidal concentrationand (MFC) had been tested, theoriginal structure-activity relationship is studied, which is of directive significance to thescreening for novel antifungal compounds.