Study On Fluoroalkylation Of Uracil And Norcantharidin

Fluoride has attracted wide attention in medicine,pesticide and materials due to its unique properties.The introduction of fluorine-containing reagents and fluorine-containing blocks into drug precursors is one of the important approaches for the development of new drugs.This article takes the discovery of novel anticancer drugs as the guide,selects the important natural product structures such as uracil,uridine,norcantharidin as research objects,and explores the fluoroalkylation of these structures under photocatalysis.Finally,we studied The direct coupling reaction of aniline compounds and 1,2-dibromotetrafluoroethane in the visible light catalysis,exploring its reaction activity and the applicable scope of each substrate,the obtained product is a very important type of block,Can be used for modification of norcantharidin.Chapter 1:Difluoroalkylation of uracil:Ethyl bromodifluoroacetate,uracil and its various substrates as raw materials,dimethyl sulfoxide as solvent,tris（2-phenylpyridine）phosphonium[Ir（ppy）₃]as catalyst,hydrogen phosphate II Potassium is a base and reacted at room temperature for 24 hours by irradiation with a visible light LED lamp（blue light,12w）.This method is an efficient and simple method to realize the difluoroalkylation of uracil.It is one of the effective methods for the synthesis of uracil difluoroalkyl compounds.The advantage of this reaction is that it utilizes the cheap and easily available ethyl bromodifluoroacetate as a fluorine source,and is easy to operate.Photocatalysis has no pollution to the environment,and the substrate functional group is excellent in compatibility.The final synthesis of compounds 27.Perfluoroalkylation of Uracil:Perfluoroiodohexane,uracil as raw material,dimethyl sulfoxide as solvent,terpyridine yttrium chloride hexahydrate[Ru（bpy）₃Cl₂]as catalyst,cesium carbonate as base.The reaction was carried out at room temperature for 24 hours by irradiation with a visible light LED lamp（blue light,12w）.This method achieves the perfluoroalkylation of uracil.The advantage of this reaction lies in the use of inexpensive and readily available perfluoroalkyl iodide as raw material,easy operation,excellent compatibility of substrate functional groups,and reaction conditions still applicable to perfluoro iodobutane.The final synthesis of compounds 10.At present,further modifications and biological activities of this series of compounds are also underway.Chapter 2:Fluoroalkylation of Norcantharidin:Using maleic anhydride and furan as starting materials,the norcantharidin was synthesized by the Diels-Alder method and then divided into two series of compounds:norcantharidin and methanol to obtain 5-ene norcantharidin The carboxylic acid methyl ester 11 and the compound 11 are further reacted with the fluorine-containing alcohol to obtain a nor-norhydro-cantharidin fluoride（13a-d）.Norcantharidin was hydrogenated to norcantharidin 12.Compound 12 was then reacted with fluoroalcohol to synthesize norcantharidin fluoride（17a-d）.The reaction was good by column chromatography to separate the product,calculate the yield,and finally characterize the structure of each reaction product by nuclear magnetic resonance.The final synthesis of compounds 8,Provides a good foundation for subsequent anti-tumor activity.Chapter 3:Direct Coupling Reaction of Aniline with 1,2-Dibromotetra Fluoroethane:Using 1,2-dibromotetrafluoroethane,aniline and derivatives as raw materials,acetonitrile as solvent,terpyridine yttrium chloride hexahydrate[Ru（bpy）₃Cl₂]as catalyst,sodium carbonate as base.The reaction was conducted at room temperature for 40 hours by irradiation with a visible light LED lamp（blue light,12w）.This method efficiently produces various2-bromo-1,1,2,2-tetrafluoroethylarene compounds.The advantage of this reaction lies in the use of inexpensive and readily available aniline and dibromotetrafluoroethane as raw materials,having a small amount of catalyst,a wide range of substrates,simple and convenient operation,and high reaction efficiency,and the product can be easily converted into many other 1,1,2,2-tetrafluoroethylation reagents.The final synthesis of compounds 16,the application of two compounds,The synthesized new compound can be directly linked to norcantharidin,which lays a good foundation for the subsequent synthesis of new cantharidin structure.