Synthesis Of Matrine Derivatives And Structure Identification

Matrine, an active component of chinese traditional medicine"Sophora flavescens"(S, flavescens Ait., S. alopecuroides L. and S. subprostrata Chun et T. Chen), is a representation of alkaloids from Sophora flavescens. And these kinds of plants are one of our country's traditional medicines which has a long history. They can clearing away heat, removing dampness, insecticidal activity, diuretic effect and so on. Their functions are not only so widespread but also obviously effective. The modern medical research also indicated that one of the essential components of these medicines, matrine, has a good effect on antipyretic effect, Lowing temperature, tramadol, sedation, protectting myocardial ischemia, reducing the myocardial injury, antiarrhythmic, resisting Coxsackie Virus B, and treat chronic hepatitis B, preventing liver fibrosis, inducing proliferation, differentiation, and apoptosis in tumor cell. It has initially appeared many kinds of pharmacological actions which has the new medicine development significance, and should be greatly developed in the tumor, the hepatitis B and in other diseases treatments in the future.The widespread use of matrine is limited because its water-solubility is not really ideal. However we can use some chemical ways---derivatization, transforming, active test comparing to study the structures of these active natural products, and thus make sure its activeness in structure, the toxic spot and functional group to reduce its toxicity, enhance its activeness and biological availability, and make it much safer and more effective in the application. There are some documents which have already concerned about the synthesis of matrine, but they lack the concrete response conditions and the exact amount of material used in reaction, and that the process of synthesis is too long.This article takes the Sophocarpine which was separated from the plants like S. alopecuroides L. as the leading compound, transforms its chemical constitution, enriches its species and properties. This is an important rearch area in taday's research field. Meanwhile, this is also a source for seeking new promising leading compounds and biologically active components. Therefore, the present paper uses half synthetic method to synthesize a series of matrine derivatives. The present paper research mainly constitutes the following four parts:Chapter one summarized the research progress on matrine family, and introduced the structure of it, related parameter data, and several manual synthetic methods, as well as pharmacological activities in clinical application.Chapter two has studied the synthesizing of alkoxyl-matrine with the raw material Sophocarpine. And thus it obtained two kinds of new compounds, 13α-methoxyl-mat-fine, 13α-oxyethyl-matrine. This chapter has also characterization of the product with the elemental analysis, 1D-, 2D-NMR, IR, the MS, conducted the research to the crystal structure of 13α-methoxyl-mat-rine, confirmed the stereo configuration of this kinds of matrine derivatives, finally confirmed it for the title compound. This operating method is simple, but its production rate is higher, moreover, its Synthesis environment is friendly.Chapter three has studied the sythesizing of additional series of Amino-matrine with the raw material Sophocarpine. And thus acquired three kinds of new compounds: 13α-methylamono-matrine, 13α-ethylamino-matrine, 13α-2-aminoethanolate-matrine. The chapter also has carried on the structure attribute to them through ¹H NMR, ¹³C NMR, 2D-NMR, IR, MS and the elemental analysis, confirmed them as the the title compound. This operating method is simple, but its production rate is higher, moreover, its Synthesis environment is friendly.Chapter four has plan to synthesize the 13α-hydroxyl-matrine with the raw material Sophocarpine in different conditions, but the sophocarpine is instability in the reaction which the water participation, it easy to hydrolysis, finally we had to arrive the hydrolysis Sophocarpine defined its product by ¹H NMR, ¹³C NMR, 2D-NMR, IR, mastered the relative analyses of spectrum, which laid the foundation of synthesis the title compound afterwards.Through modificating the structure of matrine derivatives, it have enriched the properties and species of matrine family. Using 2D-NMR can help accurately signification of chiral carbon atomic stereo configuration, which provides theoretical fundament for developing and filtrating new medicine that has high-tech and better pharmacology activities.