Synthesis And Biological Activity Of Quinoline Heterocyclic Compounds

Heterocyclic compounds have a wide application for its pharmacological activity and biological activity, so designing and discovering new heterocyclic compounds in drug research are of great importance. In particular, quinoline derivatives have been found possessing a strong physiological activity and pharmacological activity, such as anti-bacterial, anti-inflammatory, analgesic, anti-tumor and anti-virus etc. A number of quinoline heterocyclic compounds are important pharmaceutical intermediates or drugs and has been the subject of continued interest in drug research.Based on the value of the quinoline heterocyclic compounds, this paper focus on exploring new synthetic methods of quinoline derivatives, this paper can be divided into three parts. Firstly, generally several steps and much complicated post treatment and purification processes are necessary to synthesize quinoline heterocyclic compounds, in this paper one-pot method were used to synthesize compounds which reduce the loss of separation and purification of intermediates and products and thus improved the efficiency and productivity of the whole process. In the first part natural amino acid piece were introduced to the quinolone ring and three series novel compounds have been synthesized from amino-acid ester hydrochloride via replacing, cyclization and hydrolysis reaction. More than thirty4-oxo-3-carboxylic quinoline derivatives were obtained. All the compounds were screened against Bacillus subtilis, Staphylococcus aureus, Aspergillus, Escherichia coli and Monilia albican. The preliminary bioassay results revealed that they have medium antimicrobial activity against the above bacteria. The discovery of new active compounds will provide a reference for the research and development of quinoline drugs.Secondly, this paper reported a highly efficient and facile synthesis of novel quinoline lactones under microwave irradiation and a series of quinoline lactones were designed. Eleven new quinoline lactones were obtained by subjected to microwave irradiation at an output of500W.120℃for15min. Microwave irradiation proved superior in time and operation compared to conventional synthesis. Furthermore, the preliminary activity tests showed they had a moderate activity against Escherichia coli.Thirdly, the synthetic methods of quinoline heterocyclic derivatives were expanded and an efficient and environment-friendly enzymatic synthesis was developed, seven quinolines were prepared in mild reaction via Friedlander synthesis. The types of catalysts, reaction solvent, catalytic amount of dose and reaction temperature were investigated, and optimized the best reaction conditions:at room temperature with lipase from porcine pancreas as a catalyst, dimethyl sulfoxide as the solvent. Compared to the traditional synthetic methods, enzymatic synthesis has the advantage of efficient, environmentally friendly, mild conditions, easily operation etc.In conclusion, in this thesis "one pot","microwave-assistant" and "enzymatic catalysis" were investigated and applied to prepare quinoline heterocyclic compounds, more than forty new quinoline heterocyclic compounds were designed and synthesized via the three methods, the structures were characterized and preliminary biological activity were test as well, the results revealed the characterization data were correct according to the structure. Moreover, its biological activity test results show that they have a certain resistance to Bacillus subtilis, Staphylococcus aureus and Aspergillus fumigatus which to some extent expanded the spectrum of the quinoline heterocyclic compounds.