Synthesis And Antimicrobial Activity Of3-CH₂CH₂COOCH₂CH₃Substituted-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 andcardiovascular medicines. Therefore, its syntheses, structures and pharmacological activitieshave been attracted wide attentions.For a long time, our laboratory has engaged in the investigation of the synthesis of1,5-benzothiazepine derivatives and the research of their antimicrobial activities.2-and3-estersubstituted in the seven-membered derivatives of1,5-benzothiazepine have been synthesizedand some special structures of these compounds showed high antimicrobial activity. Inaccordance with the principle of local modification of the drug synthesis, after changing theimine double bond, the group addition, the group replacement and the side chain length, thestructure-activity relationship is studied to find pharmacophores and better antifungalcompounds. Therefore, a series of novel3-CH₂CH₂COOCH₂CH₃1,5-benzothiazepines aresynthesized by3-substituted1,5-benzothiazepines add a carbon on3site. The synthesizedcompounds are tested for their antimicrobial activity and investigated for the structure-activity relationships preliminarily. All of the study results will be important for screeningfor novel antifungal compounds.This thesis includes the following parts:Firstly, a series of novel3-CH₂CH₂COOCH₂CH₃1,5-benzothiazepines are synthesizedby the Friede-Crafts acylation reaction, esterification reaction, aldehyde and ketonecondensation, esterification reaction, Michael addition reaction and intramoleculardehydration reaction, where different substituted benzene is used for the raw materials.Furthermore, the structures of these new compounds are determined by IR, MS,1HNMR andelemental analysis, and the stereo-structure of the products are analyzed by single crystaldiffraction method.Secondly, in this thesis, compondⅡ connects a larger group, which make aldehyde andketone condensation, Michael addition reaction and intramolecular dehydration reaction carryout in difficulty. To overcome this disadvantage, sift through the catalyst that can catalyzethese types of reaction, and optimize each step in the amount of catalyst, reaction time,reaction temperature, solvent selection and other aspects. Consequently each step has been thebest reaction conditions, and successfully obtain the target product.Lastly, antimicrobial activities of these novel compounds are researched in vitro. Comparing with the antibacterial activity of the model compound, the originalstructure-activity relationship is studied, which is of directive significance to the screening fornovel antifungal compounds.