Design,Synthesis And Biological Evaluation Of Thiazole And Isoxazole Derivatives

The nitrogen-containing five-membered heterocyclic ring is a very important structure.In the list of common fungicides newly released on the FRAC website,there are 73 kinds of fungicides containing nitrogen-containing five-membered heterocyclic structure in 220 kinds of fungicides,accounting for 33%.It can be seen that it plays an important role in the field of fungicides.Both thiazole and isoxazole belong to the nitrogen-containing five-membered heterocyclic ring,and their derivatives have a wide range of biological activities,such as antibacterial,anti-inflammatory,anti-AIDS,anti-cancer and the like.In order to obtain a compound with better antibacterial activity,the thiazole and isoxazole ring were introduced into and substituted for the triazole ring by using 1,2,3-triazole hydrazide and benzoquinone with excellent activity in the pre-laboratory synthesis.Four series were synthesized,a total of 72 heterocyclic derivatives containing a thiazole ring and an isoxazole ring,of which 68 were reported for the first time.The antibacterial activity of the compounds showed that most of the compounds have good inhibitory activity against common pathogens of plants.The specific research contents are as follows:Based on the preliminary work of the laboratory,four series of compounds were designed and synthesized,among which A series is a hydrazide-containing hydrazide structure derivative;B series compound is a thiazole ring-containing benzoquinone derivative;C series compound is different a hydrazide structural derivative of an oxazole ring;a D series compound is a benzoquinone structural derivative containing an isoxazole ring.The structure of the representative compound was verified by 1H-NMR,13C-NMR,MS and single crystal X-ray diffraction techniques.The compounds were tested for their activity against phytopatho genic bacteria.The results showed that most of the compounds had good activity,and the A series and C series compounds were more active than the B series and D series compounds.The results of antibacterial activity showed that among all the compounds,compound A3 had the best activity against Fusarium graminearum and Sclerotinia sclerotiorum,and their EC50 was 0.58 and 0.40 μg·mL-1;respectively,Compound A13 has the best activity against Rhizoctonia solani,and the EC50 reaches 0.22 μg·mL-1,which is close to the positive control Tebuconazole.In the in vivo experiment,Compound A3 showed a good protective effect against Sclerotinia sclerotiorum、Botrytis cinerea and Fusarium graminearum.At a concentration of 100μg·mL-1,the control effect of compound A3 on Sclerotinia sclerotiorum was 87.1%,and the control effect against Botrytis cinerea was 70.4%and the control effect against Fusarium graminearum was 47.8%.The activity was slightly lower than that of the positive control Tebuconazole.The structure-activity relationship analysis found that the four series of compounds have similar structure-activity relationship.When Ri is an ortho-substituted electron-withdrawing group and R2 is a para-substituted electron-withdrawing group,the compound has the best antibacterial activity.The structure-activity relationship model was constructed by 3D-QSAR,which can predict the structure-activity relationship of A series compounds well,which is consistent with the structure-activity relationship law obtained in the preliminary work of the laboratory.