Study On Structural Modification Of Coumarin And Chitosan Oligosaccharide And Antifungal Activities

In the study of new pesticide creation,it is an effective way to create new pesticides directly by using naturally biological active substances,or by modifying lead compounds to develop higher active compounds by introducing other functional structure such as heterocyclic groups or heteroatoms.Based on the domestic cheap raw material and modern synthetic technology,the new structure and simple synthesis method from naturally bioactive molecules were designed,and the candidate lead compounds were further obtained through bioactivity screening in this paper.New coumarin derivatives containing fluorine and chitosan oligosaccharide derivatives were synthesized by introducing fluorinated groups or heterocyclic rings into the molecules to coumarin and oligochitosan respectively.In addition,their antifungal activities were tested preliminarily.The main results are as follows:(1)Synthesis and antifungal activity of novel dihydrocoumarin derivatives:chromeno[3,4-c]chromen-6-onesIt contains three aspects:? Sixteen novel coumarin derivatives,7-hydroxy-7-(trifluoromethyl)-6a,12b-dihydro-6H,7H-chromeno[3,4-c]chromen-6-one s(3a-3p)were synthesized via Michael addition,transesterification and nucleophilic addition from 3-trifluoroacetyl coumarins and phenols in the presence of organic base(NEt3).Among them,eleven target compound(3a-3k)were obtained by reacting 3-trifluoroacetyl coumarins with 2-naphthol and its derivatives.On the above basis,the range of substrates was further explored for the reaction of 3-trifluoroacetyl coumarins with phenol and its derivatives,and five target products(31-3p)were obtained.Reaction conditions were optimized for the synthesis of 3a-3k in 2-naphthol series as follows:reaction molar ratio of 2a:la:NEt3=1:1.2:1.4 in DCM solvent at 45?.The optimum conditions for the synthesis of 31-3p in the phenol series were that the reaction temperature was increased to 65? in acetonitrile,and the other conditions were the same as that of 2-naphthol.?The structures of the compounds 3a-3p were characterized by modern analytical techniques.The structures of compounds 3a-3p were characterized by HRMS,1H NMR,13C NMR and IR,which indicates that the obtained compounds are completely consistent with the designed structures.The single crystals of compounds 3a and 3n were cultured in ethyl acetate.At the same time,the single crystals(3a1)of compound 3a was cultured before acidification in order to speculating the mechanism of the reaction.?Antifungal activities of compound 3a-3p was preliminarily tested.The in vitro antifungal activities of compounds 3a-3p against Fusarium graminearum and Fusarium monitiforme were investigated by mycelial growth rate method.The results showed that the 16 target compounds showed different fungal inhibitory effects.It can be seen that compounds 3b and 3e had moderate inhibitory effects of 52.2%and 58.4%on Fusarium graminearum respectively,and 40.7%and 40%on F.monitiforme,respectively,being higher than other products in this series.In the phenol series 31-3p,compounds 31 had the best biological activities of 55%against Fusarium graminearum and 84.6%F.monitiforme.The compounds,in which there is no electron-absorbing group on the 2-naphthalene molecule,but there a methoxy group on the 8-carbon(3b)or a bromo on the 6-carbon in the benzene ring of 3-trifluorobenzopyranone(3e),showed higher antifungal activity against F.graminearum and F.monitiforme.(2)Synthesis and antifungal activities of chitosan oligosaccharide thiosemicarbazone schiff base Cu(?)complex(t)It contains three aspects:?First,chitosan thiosemicarbazone(s)was synthesized by the reaction of chitosan thiosemicarbazide with 2-pyridinecarboxaldehyde,which were prepared from the one-pot reaction of chitosan oligosaccharide with CS2 and NH2NH2·H2O.Then chitosan thiosemicarbazone Cu(?)complex(t)was obtained by the reaction of chitosan thiosemicarbazide derivatives with Cu(?)salt.The structure of the synthesized compound was characterized by IR,UV,NMR,ICP and TG-DTA.?Antifungal activity of chitosan oligosaccharide Cu(?)complex(t)were tested.The in vitro antifungal behaviors of chitosan derivative Cu(?)complex(t)against three crop-threatening pathogenic fungi:Phytophthora nicotianae(P.nicotianae);Phytophthora capsici(P.capsici)and Fusarium graminearum(F.graminearum)were investigated by mycelial growth rate method.The results showed that there are better inhibitory activities against P.capsici(74.19%)and F.graminearum(66.6%)than that of P.nicotianae(56.6%).Also,the results showed that the inhibitory rate is 20.29%and 18.7%higher than that of chitosan(53.9%ang 18.7%),being against P.capsici and F.graminearum.