Synthesis, Biological Activities And 3D-QSAR Study Of α-(N-Nitro-N-Aryl) Amino Acid Ethyl Ester Urea Derivatives

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.