Structure Of Matrine Alkaloids Modified

The alkaloids refer to some organic compounds which contain nitrogen atom except proteins, peptides,amino acids and vitamin B.Recently,some alkaloids with novel structures and excellent pharmacological activities were found continuously due to the great progress in the technologies of separation,purification,structural identification and biological activity tracing.Matrine is one kind of alkaloids.However,the widespread use of Matrine is limited because the bioavailability of Matrme is not good.The placement of activity and toxicity in the structure and the functional groups can be determined through the derivatization,conversion of original structure and comparison of activity determination.It will be much more safe and effective in the application through reducing the toxicity,increasing bioavailability and activity.It is difficult to be modified due to the saturated structure of Matrine.However Sophocarpine and Matrine are very similar in structure,and the difference is that Sophocarpine has anα,β-unsaturated bond but Matrine has not.In order to enhance Matrine's pharmacological activity, new derivatives of Matrine were synthesized by modifing theα,β-unsaturated bond.There are mainly four parts in this thesis:In the first chapter of this thesis,firstly,the classification of the alkaloid and a recent study progress were summarized.The structure,the relevant parameters of properties,the application in clinic and the determination of pharmacological activity of Matrine were particularly described. Secondly,the study on the Michael addition reaction in recent years were reviewed,this part especially focused on the introduction of the catalysts and solvents.In the second chapter,based on Sophocarpine as a substrate,use the principle of the classic Michael addition reaction,we tried the nucleophilic addition of Sophocarpine'sα,β-unsaturated bond.Two new Matrine derivatives were synthsized in this course,with Sophocarpine as an electron acceptor,Ethyl acetoacetate and diethyl malonate as electron donors.The afforded products were characterized by ¹H NMR,¹³C NMR,2D-NMR,IR and MS,and determined to be the desired products.In the third chapter,in order to improve the water-solubility and bioavailability of Matrine,at the same time,in consideration of the variability of -NO₂ and -CN functional groups,electron donors which contain -NO₂ and -CN,nitroethane and phenylacetonitrile were firstly choosed,two new desired Matrine derivatives were synthsized and characterized by ¹H NMR,¹³C NMR,2D-NMR,IR, MS and element analysis. In the fourth chapter,many heterocyclic compounds have been used in clinic due to their high molecular diversity and bioactivity.Three new desired heterocyclic derivatives of Matrine were synthsized by using indole,piperazine,pyrrole as electron donors,Sophocarpine as an electron acceptor and these compounds were also characterized by ¹H NMR,¹³C NMR,2D-NMR,IR,MS and element analysis.Finally,the full text was summarized.