有机化学 ›› 2018, Vol. 38 ›› Issue (11): 3112-3117.DOI: 10.6023/cjoc201804044 上一篇    下一篇

研究简报

新型2-(取代苄硫基)-5-(4,6-二甲基嘧啶-2-硫甲基)-1,3,4-噁二唑化合物的合成及生物活性

汪洲洋a, 徐涵靖a, 赵建平b, 刘幸海a, 翁建全a   

  1. a 浙江工业大学化学工程学院 杭州 310032;
    b National Center for Natural Products Research, University of Mississippi, Oxford, MS 38677
  • 收稿日期:2018-04-25 修回日期:2018-06-24 发布日期:2018-07-05
  • 通讯作者: 翁建全 E-mail:jqweng@zjut.edu.cn
  • 基金资助:

    国家自然科学基金(No.30900959)和浙江省自然科学基金(No.LY17C140003)资助项目.

Synthesis and Biological Activity of Novel 2-(Substituted-benzylthio)-5-(4,6-dimethylpyrimidin-2-thiomethyl)-1,3,4-oxadiazoles

Wang Zhouyanga, Xu Hanjinga, Zhao Jianpingb, Liu Xinghaia, Weng Jianquana   

  1. a College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032;
    b National Center for Natural Products Research, University of Mississippi, Oxford, MS 38677
  • Received:2018-04-25 Revised:2018-06-24 Published:2018-07-05
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 30900959) and the Zhejiang Provincial Natural Science Foundation (No. LY17C140003).

为寻找新型杂环活性化合物,通过活性亚结构拼接方法,以硫脲和乙酰丙酮为起始原料合成4,6-二甲基嘧啶-2-硫醇,随后经醚化、肼化、环化反应,最后与取代苄氯在微波辐射中合成得到13个新型2-(取代苄硫基)-5-(4,6-二甲基嘧啶-2-硫甲基)-1,3,4-噁二唑化合物.生物活性测试结果表明,在50 μg/mL浓度下,部分化合物对尖孢炭疽病菌、枸杞炭疽病菌、草莓炭疽病菌具有较好的杀菌活性,其中取代基为3-氟时对尖孢炭疽病菌的抑制率达到80.22%;若干化合物还表现出良好的抗杜氏利什曼原虫活性,其中取代基为3-氯,4-溴,3-氟和4-叔丁基时,IC50值均低于25 μg/mL,优于对照药剂巴龙霉素.

关键词: 嘧啶环, 1,3,4-噁二唑, 硫醚, 合成, 杀菌活性, 抗杜氏利什曼原虫活性

In order to find novel biologically active heterocyclic compounds, thirteen new 2-(substitutedbenzylthio)-5-(4,6-dimethylpyrimidin-2-thiomethyl)-1,3,4-oxadiazoles were prepared with thiocarbamide and 2,4-pentanedione as the staring materials via cyclization, etherification, hydrazination, cyclization and finally a benzylation reaction under microwave irradiation condition. The preliminary bioassay results indicated that some target compounds exhibited good inhibition activity against Colletrotichum acutatum, Colletrotichum gloeosporioides and Colletrotichum fragariae at 50 μg/mL, and the inhibition rate of the compound with 3-fluoro against Colletrotichum acutatum reached 80.22%. Several compounds also showed that good antileishmanial activities against Leishmania donovani, the IC50 values of those compounds with 3-chloro, 4-bromo, 3-fluoro and 4-tert-butyl substituent respectively were all less than 25 μg/mL and were more active than the control drug paromomycin.

Key words: pyrimidine moiety, 1,3,4-oxadiazole, thioether, synthesis, antifungal activity, antileishanial activity