Construction And Antifungal Activity Evaluation Of Chiral Fluorinated Cyclic Compounds

"Hunger breeds discontentment","Food depends on the land to grow,but food productivity depends on the development of technology",the pesticide is an indispensable factor of production in modern agriculture.To purposefully regulate,control and influence the relationship between plants and pests,it is necessary to adhere to the green development,green research and green use of pesticides.Recently,the fields of chiral and heterocyclic chemistry have been developed rapidly.The commercialized chiral pesticides have been regarded as a powerful tool to control plant diseases.In addition,due to the unique electronegativity and lipophilicity of the fluorine atom,the introduction of fluorine atoms into the backbones of natural products and chiral drugs could endow the compounds with broad bioactivities.It has been reported that the ratio of fluorine-containing pesticides is up to 35% among the current pesticides.At the same time,the enantioselectivity is significant to improve the bioactivities of a chiral drug.Thus,design and synthesis of chiral fluorine-containing heterocyclic and alicyclic compounds is critical for the discovery of new green pesticides.However,it is challenging to develop a directly synthetic methodology of constructing the fluorinated cyclic compounds.In this thesis,we developed two asymmetric cycloaddition strategies to rapidly and efficiently synthesize a series of chiral fluorine-containing tetrahydropyrrolidine and cyclobutane derivatives.Furthermore,we systematically tested the biological activities of the two types compounds by bacteriostatic tests on several important plant pathogenic fungi,and some compounds showed broad spectrum antifungal activities.This result shed light on a new strategy for constructing of fluorine-containing pesticides.The specific research contents are as follows:1.We designed a copper-catalyzed asymmetric [3+2] cycloaddition of methyleneamine ylides to fluorine-containing styrenes,and successfully achieved the rapid construction of chiral fluorine-containing pyrrolidines.This method has the advantages of wide substrate range,high efficiency,high stereoselectivity,etc.The isolated yield and stereoselectivity are up to 96% and 97% respectively,and the diastereomer ratio is more than 20:1.Furthermore,the antifungal experiment manifested that many compounds showed good activities against Sclerotinia sclerotiorum,Brown-rot fungi,Pestalotiopsis and Rhizoctonia solani.At the same concentration,some compounds can obtain biological activities comparable to commercial pesticides(EC 50 as low as 10.17 mg/L),indicating the practicality and potential application value of this strategy.We found that the bacteriostatic activity was significantly reduced after the removal of fluorine atoms from the structural fragment,which confirmed the important role of the fluorine atom.2.We achieved the photocatalytic asymmetric [2+2] cycloaddition of α,β-unsaturated ketones and fluorine-containing styrenes by using chiral rhodium catalysts.Accordingly,we successfully constructed a series of novel chiral monofluoro,Difluoro,trifluorocyclobutane derivatives.The fluorine-containing cyclobutane derivatives have high yields(up to 97%),good diastereomeric ratios(d.r.=1:1.1-5.3),and excellent enantioselectivities(up to 98%).It has many continuous stereocenters and continuous chiral centers containing fluorine atoms,which has great practical value.Although the antifungal activity of these compounds was poor,the fluorine-containing cyclobutanes are very useful in medicine,we will further explore the potential biological activities of these compounds through cell and virus experiments.The relevant biological activity experiments are in progress.