Synthesis of substituted novel quinazolinone compounds
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摘要: 目的 优化取代喹唑啉酮类化合物的合成工艺,重点考察温度、时间2个因素对关键中间体化合物合成的影响。 方法 平行试验比较温度、时间和缩合剂催化酯键的氨解反应,并对试验结果进行整体化分析;采用正交设计的方差分析考察反应物、温度及时间对收率的影响。 结果 和 结论 所得化合物的结构经过1H NMR、MS和13C NMR等方法确证,当反应温度为30 ℃,反应时间为24 h,缩合剂(DCC)与反应物的投料比为1.5:1时,酯键氨解反应的收率最高(65.41%),使得取代喹唑啉酮类化合物的合成路线更加符合工业生产的要求。体外抗真菌活性实验结果表明,所测定的先导化合物对5种临床致病菌都具有潜在的抗真菌活性,值得进一步研究。Abstract: Objective To optimize the synthesis route of substituted quinazolinone and investigate the influence of temperature and time in the synthesis of key intermediates. Methods A parallel test was carried out to compare temperature, time and the ester bond ammonolysis of condensing agent, including the total analysis of experimental result. And orthogonal experimental design was used and the influence of temperature and time on the yield were investigated. Results and Conclusion The structure of the compound was confirmed by 1H NMR, MS and 13C NMR. When the reaction temperature was 30 ℃, the reaction time was 24 h with the condensing agent (DCC) and the reactant ratio of 1.5:1, the yield of ester bond ammonolysis was higher. The optimal preparation procedure of quinazolinone compounds was more available for industrial production. In vitro antifungal activity test Results showed that the lead compounds measured on five clinical pathogenic fungi have the potential antifungal activity, and are worth for further study.
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Key words:
- quinazolinone compound /
- synthesis /
- orthogonal design /
- analysis of variance
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