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研究论文

含6-氟喹唑啉片段的新型1,3,4-噁(噻)二唑类衍生物的合成及抗菌活性研究

石军, 罗娜, 丁慕晗, 李传会, 万苏然, 李培甲, 李君荭, 鲍小平   

  1. 绿色农药与农业生物工程国家重点实验室培育基地 教育部绿色农药与农业生物工程重点实验室 贵州大学精细化工研究开发中心 贵阳 550025
  • 收稿日期:2020-07-29 修回日期:2020-08-11 出版日期:2030-01-01 发布日期:2020-09-16
  • 通讯作者: 鲍小平 E-mail:baoxp_1980@aliyun.com
  • 基金资助:
    贵州省自然科学基金(20201Z025),贵州省教育厅科技拔尖人才支持计划项目(2018038)和贵州省高层次留学人才创新创业项目(201809)

Synthesis and Antimicrobial Activities of Novel 1,3,4-Oxa(Thia)diazole Derivatives Containing the 6-Fluoroquinazoline Moiety

Shi Jun, Luo Na, Ding Muhan, Li Chuanhui, Wan Suran, Li Peijia, Li Junhong, Bao Xiaoping   

  1. State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang 550025
  • Received:2020-07-29 Revised:2020-08-11 Online:2030-01-01 Published:2020-09-16
  • Supported by:
    Supported by the Natural Science Foundation of Guizhou Province (20201Z025), Young Top-Notch Talent Support Program of Guizhou Provincial Education Department (2018038) and Guizhou Provincial High-Level Overseas Talents Innovation and Entrepreneurship Program (201809).

为寻找高效农用抗菌先导化合物,本文通过活性亚结构拼接法设计合成了50个含6-氟喹唑啉片段的新型1,3,4-噁(噻)二唑类衍生物6a~6y8a~8y,其结构经1H NMR、13C NMR和HRMS手段进行了表征,且化合物6i8x的结构最终由X射线单晶衍射法加以确认。初步抗菌测试表明,部分化合物表现出较好的体外抗真菌活性。在50µg/mL浓度下,化合物6b6d6t6v6x对小麦赤霉病菌的抑制率分别为58%、58%、55%、63%和60%,化合物6v8v对苹果腐烂病菌的抑制率分别为71%和64%,化合物6v对油菜炭疽病菌的抑制率为72%,它们均优于对照药剂噁霉灵(分别为51%、61%和70%)。此外,部分化合物在100µg/mL浓度下也表现出一定的体外抗细菌活性。

关键词: 1,3,4-噁二唑, 1,3,4-噻二唑, 6-氟喹唑啉, 合成, 抗菌活性

To search efficient agricultural antimicrobial lead compounds, a total of fifty 1,3,4-oxa(thia)diazole derivatives (6a~6y and 8a~8y) containing the 6-fluoroquinazoline moiety were designed, synthesized and evaluated for their antimicrobial activities, based on the method of the splicing of bioactive substructures. The structures of target compounds were fully characterized by 1H NMR, 13C NMR, and HRMS spectra, and two compounds 6i and 8x were further confirmed via single crystal X-ray diffraction analysis. The preliminary bioassays revealed that some compounds exhibited a good antifungal activity in vitro. For example, compounds 6b, 6d, 6t, 6v and 6x were found to have the inhibition rates of 58%, 58%, 55%, 63% and 60% against Gibberella zeae at 50 µg/mL, respectively. Additionally, compounds 6v and 8v displayed the inhibition efficacies of 71% and 64% against Cytospora mandshurica at 50 µg/mL, respectively. Moreover, compound 6v demonstrated an inhibition rate of 72% against Colletotrichum gloeosporioides at 50 µg/mL. The above activities were all better than that of control agent Hymexazol (51%, 61%, and 70%, respectively). Finally, some compounds also showed certain inhibition potencies in vitro against the tested bacteria at 100 µg/mL.

Key words: 1,3,4-oxadiazole, 1,3,4-thiadiazole, 6-fluoroquinazoline, synthesis, antimicrobial activity