Design,Synthesis And Biological Activity Of L-Carvone Derivatives

In the process of new drug creation,the modification and transformation of natural products has always been a hot area and a relatively effective approach.L-carvone,an important natural compound,is one of the components of spearmint essential oil.It has good biological activities such as repelling insects,acaricide,and antifungal.In this study,L-carvone was used as the lead compound,through modification of the carbonyl group of L-carvone,to obtain a drug with better antibacterial activity.In addition,studies have shown that L-carvone can activate tyramine receptors in invertebrates and is an important potential lead compound for the development of new insecticides and fungicides.In this study,the insecticidal activity and tyramine receptor activation ability of synthetic compounds were tested.Through the active substructure splicing method,the carbonyl group of L-carvone is reacted to form a compound containing an oxime functional group,and then the ester structure is introduced to form a chain-like oxime ester structure compound.This study uses this method to design and synthesize a series of derivatives of L-carvone.The structures of the target compounds have been confirmed by¹H NMR,¹³C NMR,infrared spectroscopy,and high-resolution mass spectrometry,indicating that the structures of the obtained compounds are all accurate.At the same time,the optical rotation test was performed on each compound,and the optical rotation value and the specific optical rotation value were calculated,in order to more clearly determine the crystal structure of this series of derivatives.Among them,the4r（2-Br）compound was selected for single crystal culture,and the crystal diffraction structure was tested,and the single crystal structure and the crystal packing diagram were obtained,and the structure was in the trans configuration.The in vitro antifungal activities of these derivatives had inhibitory effects on five plant pathogenic fungi,namely Sclerotinia sclerotiorum,Fusarium graminearum,Pyricularia grisea,fusariuwn oxysporum and Thanatephorus cucumeris,were determined by plate inhibition zone method with the concentration of 50 mg/L as the control.Compared with the antifungal activity of L-carvone,most of the derivatives of L-carvone showed better antifungal activity.Some of the derivatives of L-carvone showed good to excellent antifungal activity against Fusarium graminearum and Sclerotinia sclerotiorum.Among them,compound 4e showed excellent antifungal activity against Fusarium graminearum and Sclerotinia sclerotiorum（4-CH₂CH₃）had the best antifungal activity against Fusarium graminearum,with the inhibition rate of92.93%.Compound 4b（3-CH₃）had the best antifungal activity against Sclerotinia sclerotiorum,with the inhibition rate of 80.00%,which was better than the control fungicide enoximate.Compounds（4e,4l,4p,4v,4w,4x,4y,4z）with good fungicidal activities against Fusarium graminearum and compounds（4b,4e,4f,4i,4k,4l,4z）with good antifungal activities against Sclerotinia sclerotiorum,which were selected for concentration reduction and re-screening test.The results showed that the EC₅₀of target compounds 4e,4l and 4y were 5.07mg/l,7.88mg/l and 7.92mg/l,respectively;the EC₅₀of compound 4b was 18.84mg/l,which indicated that L-carvone had the potential of further research and development of new fungicides.Test the stomach toxicity activity of the derivatives of L-carvone against Plutella xylostella at a concentration of 600 mg/L by the leaf soaking method.The gastric toxicity of compounds 4i,4r,and 4w to Plutella xylostella is more than 80%,and the best activity of compound 4w is 94.43%.To test the activating effect of the derivatives of L-carvone on the tyramine receptor of Plutella xylostella at 100μmol/L,it was found that compounds 4c and 4v have strong tyramine receptor agonistic activity.It provides a new tool molecule for the in-depth study of the biological functions of the Plutella xylostella tyramine receptor.