The Exploring Of N-heterocyclic Compounds Possessing Biological Activities

N-Heteroatomic compounds is an important class of heterocycles species possessing extremely rich biological activities,which play important roles in the pharmaceuticals, agricultural chemicals and natural bioactive compounds.Therefore,efficient synthesis of N-heterocycle is the focus of research interests of organic chemists.With the development of modern organic synthesis,more and more new organic synthetic methodologies have been applied in the synthesis of heteroatomic and heterocyclic compounds.In this thesis,we present the application of asymmetric organocatalysis toward the synthesis of optically active 1,2,4-triazole and oxazolidin-2-ones derivatives which possess potential biological activities.The purpose of this research is to expand the application scope of new methodologies and to synthesize biologically active heteroatomic and heterocyclic compounds.1.The reaction of 1H-1,2,4-triazole with 2-butenal has been performed in the presence of racemic,(R)-,and(S)-J(?)rgensen catalyst and benzoic acid,respectively,to prepare racemic and both enantiomeric 3-(1H-1,2,4-triazol-1-yl)butanal via iminium- ion activative mechanism.The product 3-(1H-1,2,4-triazol-1-yl)butanal was reduced and then further reacted with acyl chloride to prepare 3-(1H-1,2,4-triazol-1-yl)butyl benzoates.Ten kinds of racemic,(R)-,and(S)-triazole compounds(totally thirty) have been synthesized.Their structures were clearly verified by spectroscopic data(NMR,MS, Elemental analysis).2.The binding interactions of triazoles with CYP51 were investigated with the commercial fungicides Triadimefon and Diniconazole as standards.The influence of stereochemistry is upon the binding constants(K_d) of the cytochrome P450-dependent lanosterol 14α-demethylase(CYP51).The results showed that the(R)-,or(S)-compounds display different binding interactions with their racemic ones.3.Asymmetric synthesis of oxazolidin-2-ones derivatives via a new organocatalytic cascade reaction of chiral stable sulfur ylides with niroolefines has been described.This novel reaction gave the corresponding oxazolidin-2-ones in up to 92%ee in dichloromethane and toluene at room temperature.The absolute configuration of the products was determined by X-ray crystallography.Their structures were clearly verified by spectroscopic data.Some compounds have been preliminarily biologically investigated.