Synthesis And Agribiological Activity Of Michael-Type Thiol Adducts Of Xanthatin

Nowadays,development of efficient and low-toxic semisynthetic pesticides through structural modification of natural active substances has become an important pathway to innovate new pesticides due to their many advantages.Xanthatin,a sesquiterpene lactone derived from Xanthium sibiricum L.（family: Compositae）,exhibits many important biological properties,including antifungal,insecticidal,anti-tumor,anti-inflammatory and antiviral etc.,and is an ideal lead compound to discovery new pesticides.Therefore,a series of xanthatin derivatives were designed and synthesized by chemical derivation and their antifungal activity against four phytopathogenic fungi,insecticidal activity and ovicidal activity against Plutella xylostella were evaluated using the spore germination method,the leaf-dipping method and the immersion method,respectively.Meanwhile,the structure-activity relationships（SARs）were discussed.The main results are as follows:1.Xanthatin was extracted from the leaves of X.sibiricum and purified by silica gel column chromatography and thin layer chromatography with an extraction rate of 0.2081%.The structure was characterized by ¹H NMR,¹³ C NMR and HR-MS.2.Twenty-eight thiol-Michael adducts of xanthatin derivatives were synthesized and their structures were characterized by ¹H NMR,¹³ C NMR and HR-MS.The absolute configuration of compounds 82 q,83a and 85 were confirmed by X-ray crystallography.It was found that the carbon-carbon single bond between C₆-C₇ and C₁₁-C₁₃ was in the trans-configuration.3.The antifungal activity of all the compounds against four phytopathogenic fungi（Alternaria solani,Fusarium solani,Botrytis cinerea,Colletrichum orbicularer）were investigated using the spore germination method.The results showed that: 1)The majority of the derivatives showed excellent insecticidal activity when compared with the xanthatin.2)Particularly,almost all the compounds displayed potent antifungal activity against A.solani.3)Compounds 82 t and 82 u exhibited broad-spectrum and excellent antifungal effects against all the tested phytopathogenic fungi,while their EC₅₀ values ranged from 7.21 to 75.88 μg/mL.4)The preliminary structure-activity relationship showed that the introduction of a pyridine group in the C₁₃ position of xanthatin can significantly increase its inhibitory activity.4.The oral toxicity of the target compounds against the late 2nd-larvae of Plutella xylostella were investigated using the leaf-dipping method.The results showed that xanthatin demonstrated potent larvicidal activity against P.xylostella larvae(LC₅₀ = 12.00 μg/mL).However,the larvicidal activity of all the derivatives were decreased when compared with the xanthatin.These findings revealed that the exocyclic double bond of these compounds might be a critical functional group for their larvicidal activity.5.The egg-hatching inhibitory activities of synthesized compounds against the one-day-old eggs of P.xylostella was determined by the immersion method.The majority of the compounds showed significant ovicidal activity,especially the compound 82 b exhibited excellent ovicidal activity(LC₅₀ = 14.04 μg/mL).Furthermore,the structure-activity relationship analysis showed that the introduction of-（4-CH₃）Ph group can significantly increase the ovicidal activity.In conclusion,twenty-eight thiol-derivatives of xanthatin were designed and synthesized.Compounds 82 t and 82 u exhibited broad-spectrum and excellent antifungal activity,and 82 b showed significant ovicidal activity.Based on these findings,this work can provide experimental basis for further exploration and utilization of X.sibiricum resources and development of new antifungal or insecticidal agents.