Synthesis And Biological Evaluation Of Novel Pyrrolic Amide Derivatives As Potential Fungicide

Due to the structural diversity,bioactivity,and environmentally compatibility,natural products could be great resource for pesticidal compounds.From the direct usage as pesticides in the early days to the application as lead compounds nowadays,natural products are closely related to pesticide development.Developing pesticides using natural products as lead compounds has many advantages:firstly,it usually features rapidity and economy;secondly,these analogs can better meet the requirements of green pesticides and sustainable development.Bromopyrrole alkaloids in sponge exhibit good biological activity and moderate molecular weights,and are ideal lead compounds for pesticide discovery.According to the biological activity of bromopyrrole alkaloids and the activity optimization strategy of natural compounds,24 kinds of pyrrolidine amide compounds with antibacterial activity were designed and synthesized.Reaction conditions for the conversion of pyrrole amide compounds to pyrrolopyrazinone were optimized,and water was used as solvent instead of organic solvents to meet the concept of green chemistry.In the bromination reaction of pyrrole,by controlling the amount of the reaction substrate,by-products in the bromination reaction were reduced to improve the atom economy.The synthesized pyrrole amide compounds（3a-f,4a-f,5a-d,6a-d,7a,8a,9a,10a）were all confirmed by ¹H NMR,¹³C NMR and ESI-HRMS.Antibacterial activities of the synthesized compounds was determined against common pathogens on rice（Magnaporthe grisea）and vegetables such as cucumber（Botrytis cinerea）.Preliminary results indicate that most of the synthesized compounds have good inhibitory effect on Magnaporthe grisea.Among them,7 compounds showed inhibition rates higher than 50%against Magnaporthe grisea at the concentration of 100μM;compounds 4a,7a,8a,9a,and 10a showed excellent inhibitory effects with EC₅₀ being 0.86±0.11,12.21±1.56,0.30±0.12,0.70±0.22,and 4.41±0.59 mg/L,respectively.Compounds 7a and 10a also showed excellent inhibitory effects on Botrytis cinerea,with EC₅₀ being 4.04±0.46 and 6.17±0.71 mg/L,respectively.Preliminary structure-activity relationship analysis of the fungicidal activity against Magnaporthe grisea was carried out.Results showed that when the hydrogen atom on the pyrrole ring was replaced with halogen or trifluoromethyl,the compound would exhibit higher antibacterial activity;when the compound is converted into pyrrolopyrazinone,its activity will be reduced.Besides,halogen or other electron-withdrawing group on aromatic amine will increase the activity.These results provide a basis for further structural optimization of the compounds.In conclusion,starting from the active fragment of natural product bromopyrrole alkaloids,and amide structure is widely used in pesticide molecules,a series of pyrrole amide compounds with excellent fungicidal activity was constructed and screened,which enriched the natural product-based pesticide discovery system and provided new applications of marine bromazole alkaloids.The screened compounds with high fungicidal activity can be used as lead compounds for further optimized derivation as new fungicides.