【作者】 黄影；

【导师】 陈长水；

【作者基本信息】 华中农业大学 ， 农药学， 2011， 硕士

【摘要】 取代脲类化合物具有多种生物活性,被广泛用于农药、医药、化工等行业。本文综述了取代脲类化合物作为除草剂、植物生长调节剂及杀菌剂的研究进展。随着人口的增长和人们环保意识的提高,开发“高效、低毒、无残留”的化合物是化学农药的发展趋势。在这种趋势下,氨基酸农药显示出强大的生命力。本文综述了氨基酸农药的国内外研究进展,叙述了氨基酸酯化合物在化工、农药等方面的应用,以及总结了氨基酸酯的合成方法。为了扩大筛选范围,寻找高活性、安全的化合物,本研究利用了活性亚结构连接法和生物电子等排原理,将具有植物生长调节、除草等多种活性的N-硝基芳胺基团、亚结构脲、氨基酸乙酯连接起来,设计合成了系列全新的N-硝基氨基酸乙酯脲类化合物。其结构通式如下：主要研究内容如下：1、N-硝基氨基酸乙酯脲类化合物的合成以2,4,6-三氯苯胺为原料,首先通过乙酰硝酸酯硝化,再用固体光气甲酰化,之后分别用L-氨基酸乙酯、DL-氨基酸乙酯进行氨解得到目标产物N-[(2,4,6-三氯苯硝胺)-羰基]-L-氨基酸乙酯、N-[(2,4,6-三氯苯硝胺)-羰基]-DL-氨基酸乙酯；以2,6-二溴-4-氟苯胺为原料,用浓硝酸硝化,再用固体光气甲酰化,然后氨解得到目标化合物N-[(2,6-二溴-4-氟苯硝胺)-羰基]-L-氨基酸乙酯。本论文合成了33个未见文献报道的N-硝基氨基酸乙酯脲类化合物。所有化合物的结构经IR、1HNMR和元素分析确认。2、生物活性测试采用“油菜试法”对所有目标化合物进行了植物生长调节活性测试,供试作物为水稻、油菜。生测结果表明：这类化合物在低浓度时表现出一定的生长调节作用,高浓度时显现抑制作用；其中大多数N-[(2,4,6-三氯苯硝胺)-羰基]-L-氨基酸乙酯化合物对水稻的根表现出良好的植物生长调节活性。采用“平皿法”测试目标化合物的除草活性和抑菌活性,供试杂草为稗草、红苋,试验浓度梯度为10,25,50,100,200 mg/L；测试病原菌为水稻纹枯病菌、油菜菌核病菌,试验浓度梯度为20,50,100,200 mg/L；采用DPS2000数据处理软件计算得出IC50和EC50,用于评价化合物的活性。试验结果表明：在供试剂量下目标化合物对稗草和红苋都有一定的抑制作用,而对稗草的抑制活性要优于红苋；目标化合物对油菜菌核病菌表现出良好的抑菌活性,大部分化合物的EC50值在50-100 mg/L,低于标样多菌灵(171.74 mg/L)和甲基托布津(154.59 mg/L)。3、三维定量构效关系分析基于相同条件下测试所得的生物活性结果,采用sybyl7.3软件对23个N硝基氨基酸乙酯脲类化合物进行了三维定量构效关系研究(3D-QSAR)。采用比较分子力场分析(CoMFA)分析N-硝基氨基酸乙酯脲类化合物结构与对稗草的除草活性之间的关系。建立了相关性好、内部预测能力可靠的3D-QSAR模型,q2=0.507,R2=0.993；得到直观地三维等势图。分析结果表明：对脲桥左侧苯环4号位引入小体积基团,而在氨基酸侧链取代基末端引入大体积的电负性基团,有利于除草活性的提高。采用比较分子力场分析(CoMFA)和比较分子相似因子分析(CoMSIA)系统研究N-硝基氨基酸乙酯脲类化合物结构与抑制油菜菌核病菌活性之间的关系。建立了可靠的模型,油菜菌核病菌：CoMFA:q2=0.630, R2=0.982, CoMSIA:q2=0.620,R2=0.957。分析结果表明：对脲桥左侧苯环4号位引入大体积的正电性基团,而在氨基酸侧链引入体积不是很大的取代基,其末端电荷顺序为负电荷接正电荷基团,利于提高化合物的抑菌活性。更多还原

【Abstract】 Urea derivatives have diverse biological activities. They have been used widely in pesticide field, medicinal field, chemistry industry and so on. In this paper, we reviewed research progress of urea derivatives as herbicide, plant growth regulator and fungicide. With the increase of population and the exaltation of the consciousness of human’s environmental protection, it is a tendency that chemistry pesticide development with "high efficiency, low toxicity, no residue". The development of amino acid pesticide is an excellent example. This paper overviewed the home and abroad research progress of amino acid pesticide, related the extensive application of amino acid ester derivatives in chemical industry and pesticide field, and summarized synthetic methods of amino acid esters. In order to look for higher biological activity compounds, we have made use of active substructure link and bioisosterism principles. We have linked the active group N-nitro aryl amine with plant growth regulating and herbicidal activities, amino acid ester group to urea substructure, retained a class of novel N-nitro amino acid ethyl ester urea derivatives. And the basic structure of them was shown:1、The synthesis of N-nitro amino acid ethyl ester urea derivatives2,4,6-trichloroaniline as starting material was nitrified with acetyl nitrate, formylated with BTC, ammonolysised with L-amino acid ethyl esters or DL-amino acid ethyl esters. N-[(2,4,6-trichlorophenylnitramine)-carbonyl]-L-Amino Acid Ethyl Esters and N-[(2,4, 6-trichlorophenylnitramine)-carbonyl]-DL-Amino Acid Ethyl Esters were prepared respectively; 2,6-dibro-4-fluroaniline as starting material was treated with the above similar processes,N-[(2,6-dibro-4-flurophenylnitramine)-carbonyl]-L-Amino Acid Ethyl Esters was synthesized.33 novel N-nitro amino acid ethyl ester urea compounds were synthesized. The structures were confirmed by IR,1H NMR and elemental analyses.2、The biological activity testThe plant growth regulating activities of all target compounds on rice, rape were tested by the "Rape hypocotyl elongation test method". The result of biological activity test showed that:the compounds show growth regulating activities at low concentration, inhibitory activity at high concentration; most of N-[(2,4,6-trichlorophenylnitramine)-car-bonyl]-L-Amino Acid Ethyl Esters express good plant growth regulating activities on root of rice."Petri dish" tests herbicidal and antifungal activities of target compounds on Echinochloa crusgalli, Amaranth and Sclerotinia sclerotiorum, Rhizoctonia solani at the concentration 10,25,50,100,200 mg/L and 20,50,100,200 mg/L respectively. The IC50 and EC50 of urea derivatives used for evaluating compound activity were caculated using DPS2000 data processing program. The preliminary result of biological activity test showed that:target compounds show inhibitory activities on Echinochloa crus-galli and Amaranth at test concentration, have better activity on Echinochloa crus-galli than Amaranth; target compounds show good antifungal activities on Sclerotinia sclerotiorum, the EC50 of most compounds are between 50 mg/L and 100 mg/L, lower than standard sample Carbendazim(171.74 mg/L) and Topstn-methyl(154.59 mg/L).3、The Three-dimensional Quantitative Structrue-Activity Relationship analysis3D-QSAR of 23 N-nitro amino acid ethyl ester urea compounds was analyzed using sybyl 7.3 program.The CoMFA method was accepted to the 23 N-nitro amino acid ethyl ester urea derivatives based on the herbicidal activity on Echinochloa crus-galli, the quantitative structure-activity relationship was studied. The credible 3D-QSAR model was established, q2=0.507, R2=0.993; the visible three-dimensional potentiometric maps were obtained. The results indicated that it is favorable to enhancing the herbicidal activity when the smaller capacity group was introduced to the 4-position of benzene ring which was on the left of urea-bridge or the bigger capacity electronegative functional group was linked to amino acid side chain terminal.The CoMFA method and CoMSIA method were applied to the N-nitro amino acid ethyl ester urea derivatives based on the antifungal activity against Sclerotinia sclerotiorum, to study 3D-QSAR. We obtained reasonable models with good predictive ability, CoMFA:q2=0.630, R2=0.982, CoMSIA:q2=0.620, R2=0.957. The results from investigation suggest that the antifungal activity of the urea derivatives become higher when the bigger capacity electropositive group was leaded to the 4-position of benzene ring which was on the left of urea-bridge or the bigger capacity group with the electronegative and electropositive terminal was introduced to amino acid side chain.更多还原