Synthesis And Antifungal Activity Of Piperine-based Derivatives

Lead optimization of natural products is an effective way and a hot area for the development of agrochemicals.Piperine is a natural amide compound with various biological activities.Plant essential oils are a class of secondary metabolites of plants,and by transforming and modifying their structures with chemical synthesis methods,derivatives with novel structures,enhanced stability and increased potency could be obtained.In this paper,the molecular structure of piperine is used as a template,essential oil and small amine molecules are introduced in the side chain of piperine to obtain compounds with better antifungal activity.The specific research is as follows:1.The structural characteristics and biological activities of piperine and essential oil compounds are comprehensively analyzed.Introduce small amine molecules and active groups of plant essential oil into the skeleton of piperine,and explore the effect of the number of double bonds on the biological activity of the compound by changing the length of the aliphatic hydrocarbon chain（ie the number of carbon-carbon double bonds）,26 piperine-oriented derivatives are designed and synthesized,5 piperine-oriented amide derivatives and 21 piperine-oriented essential oil derivatives.The target compounds are all confirmed by ¹H NMR,¹³C NMR,and LC-MS.2.The in vitro antifungal activity of the above two types of target compounds and representative intermediates against six common plant pathogens was tested using the plate method,with piperine、commercial fungicides carbendazim and azoxystrobin as positive controls.（1）For piperine-oriented amide derivatives,preliminary screening data show that the antifungal activity of most of the compounds is not as good as piperine,and some compounds such as I-3 and I-5 are equal to piperine and positive control Azoxystrobin.Compound I-3 is equivalent to piperine and slightly smaller than Azoxystrobin in the inhibition of Alternaria tenuis Nees.The overall antifungal effect is not as good as the second series of essential oil derivatives.（2）For piperine-oriented essential oil derivatives,preliminary antifungal activity screening results show that at 100μg/m L,most compounds have better antifungal activity than piperine,and some compounds have higher inhibition rates than the positive control Carbendazim.In particular,compound 2b showed 100%inhibitory activity against Phytophthora capsici,which is significantly higher than piperine（41.88%）and Carbendazim（34.27%）.Furthermore,it also has 100%inhibitory activity against Phomopsis adianticola,far better than piperine（29.63%）.From the overall data,it can be concluded that compound 2b has good antifungal activity against all six fungis.The rescreening test results showed that 2b(IC₅₀ 7.79μg/m L)had significantly better inhibitory activity against Phytophthora capsici than piperine(IC₅₀ 34.87μg/m L)and carbendazim(IC₅₀ 114.42μg/m L).It has the value of further study as a leading structure.