Synthesis And Biological Activity Evaluation Of Trichodermin Derivative As Novel Efficient Fungicides

With the Environmental Protection consciousness increasing, heavily useof highly toxic and residue pesticides has made the negative impact onagricultural production and ecological environment, which has causedworldwide concern. Many countries and certain international organizationshave developed policies to prohibit or restrict the use of highly toxic andresidue pesticides, and the world rush to invest, research and development ofnew biological pesticides. To develop and use the biological pesticides withthe characteristics of narrow anti-bacterial spectra, low toxicity for non-targetorganisms, good environmental compatibility, unique mechanism, lowcross-resistance and resistance, has become the need of the times. Nowadays,Such as the fungicide Validamycin derived from microbial metabolites hasbecome the most active and potential pesticides in the market.Trichoderma is a very important series of endophytic fungi within theplant of biocontrol agents. It’s widely used attributed to the trichodermin, itsmajor metabolite，which have broad spectrum antibacterial activity. To furtherstudy the metabolites of Trichoderma，and the better use of Trichoderma, butalso to seek a more excellent structural skeleton and more efficient and lowtoxicity of novel pilot microbial pesticide, in this paper, we consider theTrichodermin, the metabolite of Trichoderma taxi sp. nov. as the leadcompound, according to the methods of the active sub-structure connection and row principle of bio-electronics, do a more comprehensive structuralmodification and biological activity screening to Trichodermin. In this thesis,we report the following results:1) The researches of Trichodermin in an endophytic fungus, weresystematically reviewed, and the bioactive application, the fermentation,structure and bioactivities of the secondary metabolite, Trichodermin werealso investigated in detail.2)89new derivatives of Trichodermin were synthesized by modifyingthe positions of the C4, C8，C16and epoxide moiety and85of them are newcompounds. All of these compounds were confirmed by1H NMR, MS, sometitle compounds were detecte by optical rotation,13C NMR and IR, andcompound3b-10was confirmed by X-ray.3) According to Stand operation process of testing pesticidalbioactivity, a series of novel compounds with good antifungal activities weregotten: at10μg mL^-1, the compounds2a and2b had significantly higheractivities than lead compound Trichodermin in inhibiting Blumeria graminis,and inhibition rates of both reached100%; The antifungal activities ofcompounds2b,2c,2f and2i against Botrytis cinerea, were80.3%,80.3%,80.3%and87.6%, respectively, slightly lower than the lead compoundTrichodermin; Trichodermin and6d had the highest activities againstedRhizoctonia solani and antifungal activities were both100%, while antifungalactivities of compounds2i,3c-2,6f and6j were80.0%,90.0%,90.0%,80.0%,respectively; The inhibition rates of compound3b-1and Trichoderminagainsted Sclerotinia sclerotiorum were both100%, but compounds3c-2and6e were both74.8%, slightly lower; Most target compounds with mediumactivities against Ustilaginoidea oryzae, especially compounds2p,2m,3c and3c-7, the antifungal activities were68.4%,73.5%,64.9%64.9%, all were higher than the lead compound Trichodermin, which had33.8%inhibitionrate.Interestingly, compound3c-2has good potential to develop as abroad-spectrum antifungal pesticide. The EC50of it on Rhizoctonia solani is2.02μg mL^-1, that is better than the lead compound Trichodermin andcommercial fungicide Propiconazole. Moreover, the bioactivity of compounds6d and6f are better than Propiconazole, although the EC50of compounds6dand6f are only4.27μg mL^-1and4.51μg mL^-1on Rhizoctonia solani, a littleless than Trichodermin. On the other hand, compound3b-1has mediumantifungal activity, and it’s EC50value against Sclerotonia sclerotiorum is4.41μg mL^-1, but less than the commercial fungicide Carbendazim (EC50value is0.14μg mL^-1). Therefore，the new compounds3c-2,6d,6f and3b-1can beused as the second lead compounds for further structural optimization ordirectly used as a potential active substance for the development of newsesquiterpenes broad spectrum and efficient fungicides, with the value offurther research.