Studies On The Synthesis And Bioactivity Of Novel Substituted Isoxazoline And N-Methylisoxazolinium-Salt Derivatives

Isoxazole and isoxazole derivatives is one class of important heterocyclic compounds,it is not only important synthon and intermediates in organic synthesis,but also has a wide range of pharmacological and biological activities,such as pain-relief,anti-inflammatory, anti-tuberculosis,anti-convulsions,antibacterial,exciter nerve,treatment of Alzheimer's disease and take good effect on regulating calsium.Isoxazole derivatives,the hot spot of bioactive research of heterocyclic compoundes containing nitrogen,has been developed as fungicides,herbicides,pesticides and other agro-chemicals.In order to realize combination of multiform active ingredients,firstly,we designed and have synthesized a series of novel isoxazole derivatives which not reported in any litrrature via 1,3-dipolar cycloaddition reaction of N-arylmaleimides and the nitrile oxide generated in situ from the hydroximoylchloride derived from 2,3-O-cyclohexyliden-D-glyceraldehyde. Secondly,Polyhydrxyisoxazoles have been synthesized using the deprotection of first step products.thirdly,Isoxazolinium salts have been synthesized by means of methylation of isoxazole on the isoxazole ring.It extended the research field of such compounds and provided abundant leading compounds for later selecting work of effective drugs and tested the first step compounds' bioactivity in cell division cycle 25 A and leucocyte common antigen(CD45) models,the structures of target compounds were estiblished by elemental analysis,~1H NMR,IR data.This thesis consists of two major parts:The first part is about literature review.The progress in application and synthesis of isoxazoline and isoxazolinium salt derivatives。The second part is about experimental content.Major work as follows:1.Synthesis of novel 3-(1',2'-O-cyclohexylidendioxyethyl)-5-aryl-3a,6a-dihydro-4,6-dioxo -pyrrolino[3',4'-d]isoxazole derivatives by 1,3-dipolar cycloaddition reaction of JV-aryl-maleimides and the nitrile oxide generated in situ from the hydroximoylchloride derived from 2,3-O-cyclohexyliden-D-glyceraldehyde prepared using D-mannitol as starting material.2.Synthesis of novel 2-methyl-3-(1',2'-O-cyclohexyIidendioxyethyI)-5-aryl-3a,6a-dihydro-4, 6-dioxo-pyrrolino[3',4'-d]isoxazolinium chloroferrate derivatives by N-methylation of 3-(1',2'-O-cyclohexylidendioxyethyl)-5-aryl-3a,6a-dihydro-4,6-dioxo-pyrrolino[3',4'-d]-isoxazole which using the reaction of isoxazoline and dimethylsulfate.3.Synthesis of 3-(1',2'-dihydroxy ethyl)-5-aryl-3a,6a-dihydro-4,6-dioxo-pyrrolino[3',4'-d]-Isoxazole derivatives via deprotection of 3-(1',2'-O-cyclohexylidendioxyethyl)-5-aryl-3a, 6a-dihydro-4,6-dioxo-pyrrolino[3',4'-d]isoxazole in the condition of 6M HCl.