Synthesis And Antibacterial Activity Research Of(iso)oxazole Coumarin Derivatives And Pyrazole Coumarin Derivatives

The main means to control and prevent agricultural diseases is use chemical pesticides.Chemical pesticides play an indispensable role in ensuring food production.However,chemical pesticide residues cause pollution to soil and water resources.Pollutants enter the ecological cycle system to affect the health of humans and ecological environment.At the same time,the aggravation of resistance to diseases,insects,and weeds has challenged the use of existing chemical pesticides.The continuous creation of green,efficiently,highly selective,low-toxic,and low-residue new pesticide is one of the main means to deal with this challenge.Modification and transformation of the structure of natural active compounds that are highly compatible with the environment is an important way to create new green pesticides.Coumarin,whose scientific name isα-Naphthyl ketone oxygen,is widely present in roots,stems,leaves of plant and its secondary metabolites.It has variety biological activities such as anti-inflammatory,anti-bacterial,anti-cancer,and anti-oxidation.Pyrazole,oxazole,and isoxazole are widely present in natural active molecules with anti-viral,anti-oxidant,anti-bacterial,and anti-inflammatory effects,they are also important active molecular fragments in many pesticide molecules.We takes common plant pathogenic fungi as the research object,the natural product coumarin is used as the leading molecule.Then introduced oxazole,isoxazole and pyrazole into the coumarin molecule template by using active substructure splicing and bioelectronic isosteric substitution methods.Totally designed and synthesized 55 components and then conduct antibacterial activity research on all target compounds.The main work includes the following four parts:1.Series A target compounds was using salicylaldehydes with various substituted as raw materials and react with ethyl acetoacetate to synthesize a series of 3-acetyl coumarin parent rings,and then undergo Kornblum oxidation andα-amino acid cyclization to synthesize 20oxazole coumarin derivatives.2.Series B target compounds was using salicylaldehydes with various substituted as raw materials and react with 4-hydroxy-6-methyl-2H-pyrone to undergo Knoevenagel condensation reaction to synthesize a series of coumarin parent rings with enol structure,and finally with hydroxylamine hydrochloride ring closure synthesis of 19 isoxazole coumarinderivatives.3.Series C target compounds was using salicylaldehydes with various substituted as raw materials,with 4-hydroxy-6-methyl-2H-pyrone and hydrazine in a reflux one-pot method to prepare 16 pyrazole coumarinpyrazole derivatives.4.With the commercial reagents Osthole and Boscalid as the control drugs,all target compounds were tested by mycelial growth including that Alternaria solani,Botrytis cinerea,Fusarium graminearum,Rhizoctonia solani,Colletotrichum lagenarium,Alternaria alternata.The preliminary screening results showed that under the condition of a drug concentration of 50μg/m L,the target compounds showed different sensitivity to 6 kinds of plant pathogens,and all compounds had better inhibitory effects on rice sheath blight pathogens.The virulence test showed that compound C-2 has a good control effect on most bacterial species,especially it has a high inhibitory activity against Alternaria solani.The EC₅₀ value of C-2 against Alternaria solani is 4.50μg/m L is much lower than Boscalid（15.31μg/m L）and Osthole（17.33μg/m L）.It can be used as potential lead molecules to provide references for further research.