Synthesis, Spectroscopy And Coordination Chemistry Of Mannich Base Derivatives Of Kaempferol

As a group of natural polyphenolic flavonoids, flavonols exhibit a broad range of biochemical and pharmacological activities such as anti-oxidation, antitumor, antiviral, cardiovascular protection, and anti-alzheimer. Their coordination chemistry attracts more and more interest. Several novel lead compounds of flavonol have been rationally designed and synthesized in the past few years. Little attention, however, has been focused upon nitrogen containing derivatives such as flavonol mannich base probably due to the limited synthetic method with low yield and difficult separation. The research of synthetic method and mechanism of mannich derivative of flavonol can not only enrich synthesis chemistry of nitrogen containing flavonoid, but also be of great significance to the research of efficient lead compounds. This thesis focuses on the theoretical and experimental research on the synthesis, reaction mechanism, and fluorescence and ultraviolet-visible absorption spectra of a series novel mannich derivatives from naringin and their complexes.The first part of this thesis provides a detailed introduction on the basic overview of the classification, biological and pharmacological activities, chemical synthesis and spectrum of flavonoids and kaempferol derivatives, followed by the research strategy and plan proposed in the end of this chapter.In the second chapter, mannich base derivatives of kaempferol are synthesized by mannich reaction and amine exchange reaction, which not only improve the condition, rate and yield of reaction, but also provide some compounds that cannot generate directly by single mannich reaction. At first, five mannich bases and its hydrochlorides are synthesized through mannich reaction of kaempferol materials with the secondary amine. Furthermore, eight secondary amine containing flavonol derivatives are synthesized by amine exchange reaction. All the synthesized compounds are fully characterized by1H NMR, IR, EI-MS and HRMS. The results show that the geometry and nucleophilicity of primary amine have a great influence on the reaction rate and yield of the amine exchange reaction conforming to the SN2mechanism which is also supported by the further theoretical analysis of transition state.In the third chapter, UV-vis and fluorescence spectroscopy of kaempferol derivatives are studied in ethanol under acidic, alkaline and neutral conditions. The results show a maximum absorption peak of kaempferol derivatives at about370nm in the neutral ethanol which appears around430nm in alkaline medium with a bathochromic shift of60nm. The fluorescence of Kaempferol derivative in alkaline medium is far stronger than those in acidic and neutral mediums.Finally, the coordination chemistry of kaempferol derivatives is studied. Kaempferol ligand coordinates metal ions by cinnamacyl group. Bathochromic shifts are generally found in all complexs, and the peak of369nm corresponding to the ligand’s band I shifts ca.70nm to the long-wavelength regions. Composition ratio and stability constants of kaempferol derivative complexes are calculated by concentration gradient method. The order of magnitude is about106. Moreover, most complexes emit strong blue green light with the maximum emission wavelength at about482nm, while the maximum emissions of Yb and Tm are at about533nm, which red shifts50nm than that of other complexes.In conclusion, the synthetic method could provide theoretical and experimental basis for further design and synthesis of the lead compound of kaempferol drug. The research on spectrum could be beneficial to analyze the interaction bewteen flavoniod ligands with metal ions, DNA and enzymes in body.