Design, Synthesis And Biological Activity Of Adamantyl Oxadiazole Derivative

Because of the word’s ever-increasing population,modern agriculture is forced to improve the comprehensive production capacity,thereby promoting grain production and improving the quality of agricultural products.Especially,green pesticides are important strategic materials to ensure the global food security and ecological security.According to incomplete statistics,the application of pesticide plays an essential and irreplaceable role in modern agriculture,thus restoring approximated 30%of total output of agricultural products annually.In recent years,with the continuous changes in agricultural farming systems and ecological conditions,plant bacterial diseases are becoming the second fatal disease behind fungal infection and seriously jeopardizing the yield and quality of crops.At the same time,few effective bactericides can manage these infections and the control effect is difficult to meet the needs of modern agriculture.Therefore,it is extremely urgent to develop novel and efficient drugs for resisting bacterial diseases.The adamantane skeleton is composed of saturated tricyclodecane and contains a cyclohexane substructure in chair conformation.It is widely used as a versatile tool in the fields of medicine,pesticides,and materials in consideration of its unique physical and chemical properties,good biological activity,biocompatibility,non-toxicity,cheap and easy to obtain.Therefore,on the basis of previous work,this project would introduce the adamantane skeleton into the bioactive 1,3,4-oxadiazole compounds to design and synthesize a series of new adamantyl-tailored oxadiazole derivatives.We expected that highly bioactive antibacterial compounds or lead structured would be discovered.Beyond that,in order to improve the physicochemical properties,efficacy and bioavailability of the highly active compounds,we would construct the supramolecular complex by host-guest interaction.The results could provide important scientific references for the discovery of new amantadine antimicrobial agents and the prevention and control of plant bacterial diseases.In this paper,the 1-adamantanecarboxylic acid was used as the starting material.Therefore,forty-five target compounds were synthesized by five-step reactions and characterized by ¹H NMR,¹³C NMR and HRMS spectra.Subsequently,the in vitro antibacterial abilities of the fabricated compounds were screened against three bacterial strains by the turbidimetric method.Bioassay results revealed that most of the target compounds showed excellent antibacterial activity against the three tested bacteria.Among them,the minimum EC₅₀ values of compounds J₃₅ and J₃₇ against Xanthomonas oryzae pv.oryzae（Xoo）were 0.91 and 0.94μg/mL,compound J₃₇ against X.axonopodis pv.citri（Xac）was 0.88μg/mL,and compound J₃₈ against Pseudomonas syringae pv.actinidiae（Psa）was 2.10μg/mL,respectively.Moreover,bioassay results revealed that the antibacterial efficacy increased by 30-50 and 35-80 times against the corresponding phytopathogens Xoo,Xac and Psa compared to commercial agents bismerthiazol and thiodiazole copper,respectively,indicating that the introduction of adamantane skeleton could improve the interaction between 1,3,4-oxadiazole compounds and pathogenic bacteria,thereby enhancing the biological activity of the target compounds.On this basis,the supramolecular complex(J₃₇@β-CD,molar ratio1:1)was constructed by the host-guest interaction,and was confirmed by ¹H NMR.The results showed that the introduction ofβ-cyclodextrin could significantly increase solubility and wettability of compound J₃₇ on plant leaves(contact angle decreased from 92.5°(J₃₇)to 86.5°(J₃₇@β-CD)),thus improving the bioavailability of the drug.This outcome affords the foundation for the next step of evaluating in vivo drug efficacy of supramolecular complexes.At the same time,this study provides theoretical support for the prevention and control of plant bacterial diseases.