| Strobilurins antibiotics have been investigated for several decades and their synthetic analogues as pesticides have flourished in the past decade. The synthesis and structural modification of strobilurins was made breakthrough in late 80s' of last century. Azoxystrobin, a synthetic strobilurin fungicide, was first discovered and successfully developed into the market. Subsequently, some other new strobilurin fungicides, such as pyraclostrobin, have commercialized, and fluacrypyrim, an acaricide, as well. The synthetic strobilurins all show a dramatically improved photostability while keeping with equal or even improved antifungal activity, giving another excellent example from modification of natural product in the history of pesticide research.The synthetic strobilurins characterized with structural diversity, especially their substructures responsible for the biological activity, including not only methoxy acrylic ester, but also methoxyiminoacetic ester, methoxyiminoacetamide and other analogous groups. Base on naturally occurring cinnamates and structurally related diarylacryl-amides, fungicides as dimethomorph had launched sales. 3-substituted amino-2-cyanoacryl esters or amides, similar to strobilurins in their major substructure, have been recently paid more attention.The dissertation focuses on novel 2-cyanoacrylic acid derivatives, including 3-substituted-2-cyanoacryl esters and amides. The structural characteristics of strobilurins, cinnamates or diarylacrylamides and 3-substituted amino-2-cyanoacryl esters or amides, would be combined in designing the title compounds.The design of structurally novel compounds originated from as follows. Firstly, acrylic acid derivatives with biologically activities, being structurally stretchable and improvable, have been paid much attention. Secondly, 2-cyanoacrylic acid derivatives as pesticidal compounds have just been staretd for investigation. Third, the research into synthetic 2-cyanoacrylic acid derivatives, to some extent, continually stretches the investigation of the natural products mentioned above. And more, the designed structures are 3-(substituted) amino-2-cyanoacrylic acid derivatives, with potential substitution of amino group and derivation of the acid.It aims at discovery research, exploring chemical and biological properties of thetitle compounds, finding novel substances or lead compounds with potential pesticidal activity, good physicochemical property and environmental compatibility through systemic chemical synthesis and biological screening.Thus total thirty-three novel compounds belonging to 2-cyanoacrylic acid derivatives, including twelve 2-cyanoacryl amides and twenty-one ethyl 2-cyanoacrylates, were synthesized and all screened through bioassay.The 2-cyanoacryl amides were prepared starting from a reaction of malononitrile and (substituted) benzoic chlorides, and resulting (substituted) benzoyl malononitriles were treated with dimethyl sulfate to give 3-methoxy-3- (substituted) phenyl-2-cyano-acrylonitriles. The 2-cyanoacrylonitriles, containing a methoxy as leaving group, underwent simultaneously both condensation and hydrolysis in aqueous solution containing primary fatty amines or ammonia, and converted to the desired compounds, 3- alkylamino -3-(substituted) phenyl -2-cyanoacrylonitriles. This synthetic method has first been reported.The reaction of ethyl cyanoacetate and (substituted) benzoic chlorides in the presence of magnesium ethylate give ethyl 3-hydroxy-3- (substituted) phenyl-2-cyano-acrylates, which were subjected to chlorination and followed by amination, obtaining the desired ethyl 2-cyanoacrylates, i.e. ethyl 3- alkylamino-3- (substituted) phenyl-2-cyanoacrylates.Twenty-six of thirty-three synthesized compounds are first reported. Among them seven were found to exhibit biologically active in some case by screening through seventeen selected target pests. 3-(4-chlorophenyl)-3-methylamino-2-cyanoacrylamide (JS3OO) exhibited herbicidal activity, and other six compounds, all belonging to ethyl 2-cyanoacrylates, are fungicidally active, including 3-amino-3-phenyl-2-cyanoacrylate (compound II-1) and their N-substituted or N, N-disubstituted analogues.Pre-emergency soil treatment at a dosage of 500 g ai/hm2, JS300 showed 70% of inhibitory to chingma Abutilon theophrasti Medic, bristlegrass Setaria viridis (L.) Beauv and common crabgrass Digitaria sanguinalis (L.) Scop. Compounds II-1, II-5 and II-9 exhibited good activity against wheat head blight Gibberella zeae. At lower dosage, II-1 and II-5 kept highly active, and even more effective than carbendazim, a popular fungicide. The compounds 11-14 to cucumber downy mildew Pseudoperonospora cubensis, and II-3 and 11-12 to rice sheath blight Pyricularia oryzaeas well.The compound II-1 was evaluated as a fungicide candidate for further investigation. Since compounds II-1 is more active than compounds II-5. In lab test, II-1 also exhibited good activity against wheat head blight G zeae, rice bakanae Fusariurm moniliforme and watermelon fusarium wilt Fusarium oxysporum. The pathogen growth inhibitory EC50 are 0.1411, 0.4592 and 3.5649 mg L"1 respectively, significantly superior to that of carbendazim. There obtained a similar result as to carbendazim resistant strains of G zeae. The compound II-l gave EC50 of 0.2252 and 0.1895 mg L"1 respectively for both sensitive and carbendazim resistant pathogens of G zeae, with relative toxicity of 248.93 and 295.83 respectively in comparison with that of carbendazim at 100.In greenhouse test, it was confirmed that II-l was effective against wheat head blight G zeae, and inhibited the disease spot up to 70%, much better than that of carbendazim as well. In field trial, II-l showed excellent efficacy to wheat head blight G zeae at a recommended dosage of 375 g ai/hm2.Further research & development of the compound II-l, as an experimental fungicide, is now in progress. Other biologically active compounds could be continually modified structurally based on primary knowledge of their structure and activity relationship. |
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