Synthesis And Antimicrobial Activities Of1,5-Benzothiazepine Derivatives Containning Heterocycles And Carboxyl Group

1,5-benzothiazepine is a kind of seven-membered heterocyclic compoundwhich has important physiological activities. Some of their derivatives have been usedin clinic as antianxiety drugs、antidepressant and cardiovascular medicines. Thiophene,furanand and other heterocycles are a class of compounds with various bioactivities,Some of which have been used as anthelmintics drug, cephalosporin drugs inclinical,some used in agriculture as pesticides, herbicides, etc. Therefore,1,5-benzothiazepine and heterocyclic compounds’ structure, syntheses andpharmacological activities always attract wide attention of human beings.There has long been engaged in the synthesis of1,5-benzothiazepinederivatives and the research of their antimicrobial activities in our laboratory. Testresults of the antimicrobial activity show that some of these compounds have goodantimicrobial effects on bacteria and fungi, which will have important significance tofind the new physiological activity and special function of drugs. Because of many1,5-benzothiazepine derivatives of water-soluble is very poor, the compounds arehard to be used for pharmaceutical synthesis. Therefore, in order to increase theirwater-soluble, a series of2-COOH substituted1,5–benzothiazepine-2-carboxylicacid are designed and synthesized in this paper. In view of thiophene, furan and otherheterocyclic compounds with some antibacterial activity,2–thiophene,furansubstitutd1,5-benzothiazepines are synthesized, expect that there will be reactivesuperimposed to get better antibacterial activity of1,5-benzothiazepine derivatives.The main job in this thesis is as follows:Firstly, a series of2-COOH substituted1,5–benzothiazepine-2-carboxylic acidare synthesized by the Friedel-Crafts acylation reaction,Michael addition reaction andIntramolecular Cyclization reaction, where different substituted benzene and maleicanhydride are used for the raw materials, and the structures of these compounds aredetermined by IR、1H NMR、13C NMR、MS and elemental analysis method.Secondly, With substituted heterocyclic aldehyde and acetylacetone as the rawmaterials, to generate the corresponding chalcone, which reaction with2- amino-thiophenol (or4-chloro-2–amino-thiophenol) to produce a series of new2-heterocyclic-3-acetyl-4-methyl-(7-chlorine)-1,5–benzothiazepine by the Michaeladdition reaction and Intramolecular Cyclization reaction. The structures of thesecompounds are determined by IR、~1H NMR、MS and elemental analysis.Lastly, antimicrobial activities of24novel compounds are researched in vitro.And on the foundation of these results, the original structure-activity relationship isstudied.