Synthesis And Antifungal Activity Of Oximes Derivatives Bearing Adamantane Moiety

Compounds containing oxime structure have good biological activities such as anti-tumor,anti-virus,insecticidal,bactericidal,etc.They have the profits of high efficiency,low toxicity,low residue and so on.Heterocyclic compounds are the hotspot of pesticide creation in this new century.As an electronic isostere of benzene,pyridine structure also has become a research hotspot.In addition,adamantane is a kind of tricycloalkane,which is highly symmetrical in the shape of cage.Therefore,adamantane structure has good thermal stability,oxidation resistance,strong fat solubility,low toxicity which tends to enhance biological activities of compounds.However,adamantane derivatives are rarely studied in the field of pesticides.Therefore,we spliced the adamantane moiety into the compound which included both oxime and pyridine structure with the method of rational drug design?also known as structure-based drug design?,then synthesized three series of 22 kinds of adamantane based compounds which were tested in vitro antifungal activity.It provides a reference for the creation of new pesticides.The main research contents and results are as follows:1.Taking the fungicide pyrifenox as a leading compound,3-methyl pyridine lost a proton and gave 3-pyridylmethyl lithium.Then 3-pyridylmethyl lithium was reacted with ethyl 1-?adamantan-1-yl?carboxylate to yield 1-?adamantan-1-yl?-2-?pyrid-3-yl?ethan-1-one.Finally,this key intermediate was reacted with appropriate alkoxyamine/benzoxyamine under the alkaline condition to afford the target compound 1-?adamantan-1-yl?-2-?pyridin-3-yl?ethan-1-one oxime ether?I?.2.The intermediate 1-?adamantan-1-yl?-2-?pyridin-3-yl?ethan-1-one is firstly converted to1-?adamantan-1-yl?-2-?pyridin-3-yl?ethan-1-one oxime by reacting with hydroxylamine hydrochloride,and then esterified with substituted benzoyl chloride to synthesize 11 kinds of1-?adamantane-1-yl?-2-?pyridin-3-yl?ethan-1-one oxime ester?II?.3.The synthesized target compounds were confirmed by IR,¹H NMR,¹³C NMR and HRMS.The physical and chemical properties of the intermediates and target compounds were analyzed and discussed in detail.The attribution of peaks of the infrared absorption spectra and nuclear magnetic resonance spectrum were determined.4.Botrytis cinerea,Sclerotinia sclerotium,Cucumber anthracis and Rhizoctonia solani were as the tested fungi.The in vitro antifungal activity against these four pathogenic fungi were evaluated,and some compounds exhibited good antifungal activity.Results showed that the target compound I had good antibacterial activity.In the activity test for Rhizoctonia solani,the EC50 values of I_d and I_g could reach 9.66 and 8.9?g/mL respectively,and the EC50 value was lower than the control agent chlorothalonil?14.11?g/mL?.The inhibitory effect of the two compounds on Rhizoctonia solani was better than that of the commercial fungicide chlorothalonil.For the inhibitory activity test of Sclerotinia Sclerotium the EC₅₀ of I_d,I_e,and I_f reached 11.25,14.04,12.87?g/mL,respectively,which were all less than chlorothalonil?14.52?g/mL?,which showed that the inhibitory effect of the three compounds on Sclerotinia Sclerotium was better than that of the commercial fungicide chlorothalonil.The target compound II showed moderate antifungal activity.