Synthesized Of Carabrone Derivatives And Their Antifugal Activities

Bioactive natural product model is a primary way to research and develop novel pesticides. Carabrone is a sesquiterpenoid compound existing in many plants,which showed high and broad-spectrum antifugal activity found by the Research and Development Center of Biorational Pesticides during the studying on the fungicidal activities of Carpesium macrocephaLum Franch.et Sav.The earlier research showed thatα-methylene-γ-lactone potentially be the main antifungal activity groups of carabrone and different substituting groups at bit-4 had different effect on the antifungal activity. In order to confirm the main antifungal activity groups of carabrone, and discuss the antifungal activities of the analogues root in the change of carabrone's bit-4, 17 carabrone derivatives were synthesized and their antifungal activities were tested .The relationship between structures and antifungal activities were analysised.The main results showed as follows:1.17.3g carabrone(L3) and 3.6g carabrol(L6) were isolated from its petroleum ether-acetone(6:1) extracts through different types of colounm chromatography, TLC and recrystallization and so on. The purity of these two compounds were 92% and 89% by the detecting of HPLC,respectively. At the same time,the compoundsβ-sitosterol (L1),telekin(L2),alantolactone(L4)and ivalin(L5)were obtained.2.Compounds 2,4-dinitrophenylhydrazone (T1), semicarbazone (T2), acidic loop-opened analogue (T3) and 13-methoxycarabrone(T4) were obtained by the modification of Carabrone and Chloro-substituted(C1)and 12 new ester analogues(C2～C13)were synthesized by the modification of Carabrol's bit-4 hydroxy and their chemical structure were confirmed by IR, 1HNMR,13CNMR and ESI-HRMS.3. Hanging drop method were used to assay the biological activities of the derivatives and the Bioassay Results indicated that the inhibition effect of analogues T1 and T2 improved by three and two folds compared with Carabrone ,on the contrast the inhibition effect of analogues T3 , T4 and C1 were obviously decreased,especially the analogues T3. The ester analogues showed obviously different inhibition effect. Among which, the inhibition effect of analoguesC7,C13 were no obviously difference on carabrone and the rest ester analogues were showed lower antifungal activity than the carabrol .4.Analyzing activities and structure characters of ester analogues,some definite rules between the structure and activity of carabrone and it's derivatives were found:first, the nitryl at the contraposition of phenyl was contribute to the antifungal activity and the methoxy at the contraposition of phenyl decended the antifungal activity, second, the longer linear chain alkane was the higher the antifungal activity of the analogues showed ,third, the linear chain alkane exihitbited lower antifungal activity than the branched chain alkane.Because the numbers of the analogues is not enough ,the further research of the relationship between structure and activity is necessary.Based on the research above ,the main conclusion showed as follow: first, theα-methylene-γ-lactone group was the main antifungal activity groups of Carabron, second, the different substituting groups at bit-4 had obviously different effect on the antifungal activity, among which,the group contain C=N can greatly improve the antifungal activity and the group contained chlorine may decrease the antifungal activity.In order to obtain higher antifungal activity ,the group of hydrazone, acidamide and the main antifungal activity group of the existing fungicidal can be introduce in the further research. Higher antifungal activity.