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  

Synthesis and Biological Activity of Novel 1,3,4-Thiadiazole Thioether Derivatives Containing Pyrimidine Moiety

作　　者：李倩梅[1] 庞凯胜 赵建平 刘幸海[1] 翁建全[1] 

机构地区：[1]浙江工业大学化学工程学院,杭州310032 [2]National Center for Natural Products Research, University of Mississippi,oxford38677

出　　处：《有机化学》2017年第4期1009-1015,共7页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.30900959);浙江省公益性(No.2014C31127)资助项目~~

摘　　要：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,^(13)C 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50μg/m L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23.6μg/m L.In order to find novel biologically active heterocyclic compounds, fifteen novel 1,3,4-thiadiazole thioether deriva- tives carrying pyrimidine moiety were prepared by using thiocarbamide and 2,4-pentanedione as the staring materials via cy- clization, etherification, hydrazination, cyclization and the last benzylation reaction under microwave irradiation. The struc- tures of the synthesized compounds were characterized by 1H NMR, 13C NMR, IR, ESI-MS and elemental analysis. The pre- liminary bioassay results indicated that some target compounds exhibited moderate inhibition activity against Colletrotichum acutatum, Colletrotichum gloeosporioides and Colletrotichum fragariae at 50 p.g/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 Col- letrotichumfragariae 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）thiomethyl）-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.

关 键 词：嘧啶环 1 3 4-噻二唑 硫醚 微波合成 杀菌活性 抗杜氏利什曼原虫活性 

分 类 号：O626[理学—有机化学]