Study On The Structure Modification Of The Alkaloid Of Matrine

Nature Pharmacological chemistry play an important role in chemistry, especially in organic chemistry at all time, not only because the study of nature pharmacological chemistry can take tremendous challenge to organic chemists, but also because the result of which can improve people's health situation greatly, so it has a close relationship with us. As far as the study of drugs is concerned, more than one third of the clinical drugs were derived from natural products so far. There is a great variety of the resources of natural products in our country which has been applied to Chinese traditional medicine for a long time. Chinese organic chemists always regard the natural products as significant targets of research because of the ascendant conditions. The natural products of alkaloids are especially listed among the hottest point by the chemists and pharmacologists for its broadly and excellently pharmacological activities at all times.The alkaloids refer to some organic compounds which contain nitrogen atom except proteins, peptides, amino acids and vitamin B. It is a kind of pharmacologically active nature organic compounds and is earliest investigated by scientists. For the most of the compounds like alkaloids show excellent pharmacological activity, they are usually the effective components in many medical plants including many Chinese traditional medicines. The researches on alkaloids are undergoing actively in the domestic and in the foreign countries at present. Because the technology of separation, purification, character and biological activity's tracing have made great progress, some alkaloids with novel structures and excellent pharmacological activities were found continuously. The modification of alkaloids' structure which had been confirmed is an important field in the study of natural medicine. We aimed to further improve the pharmacological activities of the matrine, and some primitive modification to the structure of matrine was carried out. As a result, several novel derivatives of matrine were synthesized. This thesis comprises four parts shown as follows:In the first chapter, we summarized the studying progress of the natural medicine and the alkaloids firstly, emphasizing to introduce the new methods and ideas in the research of the alkaloids. We also introduced matrine's biological character and its comprehensive pharmacological activities in detail, and the summary of its presently studying progress was made as well.In the second chapter, for the good solubility of anticipated product we design an experiment in which sophocarpine was taken as the initiative material to be oxidized by potassium permanganate and the dihydroxylation product: 13, 14-dihydroxymatrine was given out successfully. The final product was determined by several methods.In the third chapter, according to the rule of high efficiency, atom economy in the combinatorial chemistry as well as green, zero pollution and environmentally benign idea in organic synthesis, we success to design an experiment to synthesize two novel derivatives of matrine. The method was confirmed to be a novel, high efficiency, green protocol for one-pot preparation of matrine dithiocarbamate. This protocol avoids the use of some toxic organic solvents, such as chloroform, DMF or DMSO, and some catalysts. The plausible dual role of water in promoting the reaction is rationalized by the mechanism we have described. In addition to the above advantages, the metal-free, non-hazardous and mild experimental conditions, simple experimental procedures, easy workup also show great superiority in this experiment. The desired products were confirmed by two-dimensional NMR spectrum and x-Ray single crystal diffraction anylysis etc.In the last chapter, with an attempt to apply the classic principle of Michael addition we still use the initiative material sophocarpine and try to make it as an electron acceptor and nitrocarbol or acetacetic ester as an electron donor in this reaction. The result has shown that the sophocarpine has poor reaction activity, and the yield was lower than the reaction in which the electron donor wereα,β-unsaturated aldehydes orα,β-unsaturated ketones. We broadened the application range of Michael addition reaction and get what we have anticipated through our study.