新型含嘧啶环结构的1,3,4-噻二唑硫醚类化合物的合成及生物活性
收稿日期: 2016-10-17
修回日期: 2016-12-20
网络出版日期: 2017-01-17
基金资助
国家自然科学基金（No.30900959）和浙江省公益性（No.2014C31127）资助项目.
Synthesis and Biological Activity of Novel 1,3,4-Thiadiazole Thioether Derivatives Containing Pyrimidine Moiety
Received date: 2016-10-17
Revised date: 2016-12-20
Online published: 2017-01-17
Supported by
Project supported by the National Natural Science Foundation of China (No. 30900959) and the Public Project of Zhejiang Province (No. 2014C31127).
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、环化和苄基化反应，采用微波促进方法合成了15个新型含嘧啶环结构的1，3，4-噻二唑硫醚类化合物. 利用1H NMR，13C NMR，IR，ESI-MS及元素分析对其结构进行了表征确认. 生物活性测试结果表明，在50 μg/mL浓度下，部分目标化合物对尖孢炭疽菌、枸杞炭疽菌和草莓炭疽菌具有较好的杀菌活性，其中2-（3-氟苄硫基）-5-（4，6-二甲基嘧啶-2-甲硫基）-1，3，4-噻二唑（7i）对尖孢炭疽菌和草莓炭疽菌的抑制率分别为79.84%和73.46%；若干化合物还表现出良好的抗杜氏利什曼原虫活性，其中2-（2-氟苄硫基）-5-（4，6-二甲基嘧啶-2-甲硫基）-1，3，4-噻二唑（7h）和2-（4-氟苄硫基）-5-（4，6-二甲基嘧啶-2-甲硫基）-1，3，4-噻二唑（7j）的IC50分别为21.3和23.6 μg/mL.
李倩梅 , 庞凯胜 , 赵建平 , 刘幸海 , 翁建全 . 新型含嘧啶环结构的1,3,4-噻二唑硫醚类化合物的合成及生物活性[J]. 有机化学, 2017 , 37(4) : 1009 -1015 . DOI: 10.6023/cjoc201610026
In order to find novel biologically active heterocyclic compounds, fifteen novel 1,3,4-thiadiazole thioether derivatives carrying pyrimidine moiety were prepared by using thiocarbamide and 2,4-pentanedione as the staring materials via cyclization, etherification, hydrazination, cyclization and the last benzylation reaction under microwave irradiation. The structures of the synthesized compounds were characterized by 1H NMR, 13C NMR, IR, ESI-MS and elemental analysis. The preliminary bioassay results indicated that some target compounds exhibited moderate inhibition activity against Colletrotichum acutatum, Colletrotichum gloeosporioides and Colletrotichum fragariae at 50 μg/mL, and the inhibition rate of 2-(((4,6- dimethylpyrimidin-2-yl)thio)methyl)-5-((3-fluorobenzyl)thio)-1,3,4-thiadiazole (7i) against Colletrotichum acutatum and Colletrotichum fragariae were 79.84% and 73.46% respectively. Several compounds also showed good antileishmanial activities against Leishmania donovani, 2-(((4,6-dimethylpyrimidin-2-yl)thio)methyl)-5-((2-fluorobenzyl)thio)-1,3,4-thiadiazole (7h) and 2-(((4,6-dimethylpyrimidin-2-yl)thio)methyl)-5-((4-fluorobenzyl)thio)-1,3,4-thiadiazole (7j) were found highly active with IC50 values of 21.3 and 23.6 μg/mL, respectively.
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