精油—甲氧基丙烯酸酯杂合物的设计合成及抑菌活性测定

发布时间：2019-02-16 05:29

【摘要】：精油是芳香性植物的次生代谢产物,具有抗菌、抗炎等多种活性。但是,目前国内外对精油有效成分的化学修饰和结构改造的报道并不多见。另一方面,甲氧基丙烯酸酯类杀菌剂是上世纪80年代开发的具有高效、广谱、环境友好等优势的一类杀菌剂,目前,在世界农用杀菌剂的市场上仍占有重要的份额,因此对此类杀菌剂新结构的研制仍是热门领域。本文在保留甲氧基丙酸酯类杀菌剂桥部分和药效团部分的情况下,在其侧链引入精油活性基团,以期望获得具有更好抑菌活性的化合物。具体研究内容如下:1、综合精油及甲氧基丙烯酸酯的结构特征,设计了系列精油-甲氧基丙烯酸酯杂合物。具体以邻甲基苯乙酸和邻甲基苯乙酮为起始原料制备(E)-2-(2-(溴甲基)苯基)-3-甲氧基丙烯酸甲酯等甲氧基丙烯酸酯类中间体I,进而将获得的中间体I与麝香草酚、香芹酚、丁香酚等精油单体分子进行杂合,制备目标化合物精油-甲氧基丙烯酸酯杂合物II,结构经~1HNMR、~(13)CNMR和LC-MS等分析确证。2、以嘧菌酯为阳性对照,采用体外菌丝生长速率法,选取茶拟盘多毛孢属、油菜核盘、桃褐腐、水稻稻瘟病菌等12种病菌为供试菌种,对目标化合物、精油小分子单体、中间体等进行了抑菌活性测试。结果表明:在100 mg/L浓度下,相较于阳性对照嘧菌酯,化合物II-1对油菜核盘菌等3种病原菌具有较好的抑菌活性,化合物II-2对水稻稻瘟病菌等5种病原菌显示出优异的抑制活性,化合物II-7对拟盘多毛孢属病菌等8种病原菌均表现出良好的抑菌活性,尤其是对拟盘多毛孢属病菌、桃褐腐病菌和水稻稻瘟病菌的抑制率均高于93%。在进一步的活性测试中,化合物II-2表现出很好的抑菌活性,对拟盘多毛孢属病菌、油菜核盘菌和水稻稻瘟病菌3种病原菌的EC_50值分别为0.25 mg/L、0.64 mg/L、0.96 mg/L,均优于对照药物嘧菌酯;化合物II-1、II-2、II-3、II-7对油菜核盘菌EC_50值均小于嘧菌酯的EC_50值18.75mg/L,具有进一步研究的意义。
[Abstract]:Essential oil is a secondary metabolite of aromatic plants, with antibacterial, anti-inflammatory and other activities. However, there are few reports on chemical modification and structural modification of essential oil active components at home and abroad. On the other hand, methoxy acrylate fungicides are a kind of bactericides with high efficiency, wide spectrum and environmental friendliness developed in the 1980s. At present, they still occupy an important share in the world market of agricultural fungicides. Therefore, the development of new structure of this kind of fungicides is still a hot field. In this paper, the essential oil active group was introduced into the side chain of methoxypropionate in order to obtain the compounds with better bacteriostatic activity under the condition of retaining the bridge part and the pharmacophore part of methoxypropionate fungicides. The main contents are as follows: 1. A series of essential oil-methoxy acrylate hybrids were designed based on the structural characteristics of essential oil and methoxy acrylate. The intermediates of methoxyl acrylate, such as (E)-2- (bromomethyl) phenyl) -3-methoxy methyl acrylate, were prepared from o-methylphenylacetic acid and o-methylacetophenone as starting materials. The intermediate I was then hybridized with essential oil monomers such as thymol, carvingol and eugenol to prepare the target compound essential oil-methoxy acrylate hybrid II, structure via ~ 1HNMRs. ~ (13) CNMR and LC-MS were used to confirm the results. 2. With pyridamole as the positive control, 12 kinds of bacteria, such as Chlorophyllum, Brassica, Peach Brown rot and Rice blast fungus, were selected as the tested strains by the method of mycelium growth rate in vitro. The antimicrobial activity of target compounds, essential oil monomers and intermediates were tested. The results showed that under the concentration of 100 mg/L, compound II-1 had better antibacterial activity against three pathogens, such as Sclerotinia sclerotiorum, compared with the positive control. Compound II-2 showed excellent inhibitory activity against 5 kinds of pathogens, such as rice blast fungus, and compound II-7 showed good inhibitory activity against 8 kinds of pathogens such as Trichoderma. The inhibition rate of Peach brown rot pathogen and rice blast fungus were higher than 933%. In the further activity test, the compound II-2 showed very good bacteriostatic activity. The EC_50 value of compound II-2 was 0.25 mg/L,0.64 mg/L, for the three pathogens of Trichoderma, Sclerotinia sclerotiorum and Rice blast, respectively. 0. 96 mg/L, was superior to the control drug pyridamole. The compound II-1,II-2,II-3,II-7 is of significance for further study on the EC_50 value of Sclerotinia sclerotiorum in rape, which is lower than the EC_50 value of azoxystrobin in the presence of 18.75 mg / L.
【学位授予单位】：华中农业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ455.4

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