Synthesis Of Schiff Bases And Phosphoramidate Derivatives Of Paeonol

Pae, an active ingredient of two kinds of Chinese herbal medicines, Cynanchum and paniculatum, has anti-arrhythmic, anti-atherosclerotic vein, anti-tumor, anti-inflammatory, enhancing immunity, and other varieties of pharmacological effects. The related bioactivities of Pae have drawn more research attention of Chemists and pharmacologists at home and abroad. However its poor water-solubility, volatility, unstability and the related low bioavailability limit its bio application in some extents. So many works began to focus on the biofuntional mechanism study and the structure modification of Pae for obtaining relatively high efficiency, low toxicity and bioavailability of Pae derivatives. Taking into account the physiological activities of amino acid esters and at the same time the antibacterial activity of Schiff base, a series of new Pae Schiff derivatives were synthesized by additon and elimination reaction of carbonyl group of Pae with amino group of various amino acid esters under certain conditions. The related reaction conditions were optimized. Besides, a series of Paeonol amino phosphates of piperazine-containing pharmacophore were synthesized via sphosphorylation reaction, based on the prodrug principle of drug molecules design of introducing bioactive pharmacophore of piperazine and nitrogen mustard into the Pae. The bioacivity related non-covalent interactions of some target derivatives and bovine serum albumin were also investigated by fluorescence spectroscopy and UV spectra. The specific contents are as follows:The dissertation first reviews the methods on Pae content determination, Pae extraction and isolation, Pae-related pharmacological activities and the structural modification in recent years. The template reaction using Paeonol and glycine methyl ester as reactants was then employed to optimize the related reaction conditions such as suitable solvent and molar ratios of raw materials etc. Then eight novel paeonol Schiff derivatives were synthesized under the optimized conditions and their structures were confirmed by ESI MS, IR, NMR. Moreover some structures of the new derivatives were further investigated and confirmed by X-ray diffraction. Following that, eight Paeonol amino phosphates of piperazine-containing pharmacophore were synthesized via sphosphorylation reaction of Pae with piperazine-containing, nitrogen mustard and other pharmacophore containing phosphoryl chloride. Their structures were confirmed by ESI MS, IR. NMR. The non-covalent interactions between three phosphorous containing derivatives and bovine serum albumin were investigated respectively using the fluorescence spectroscopy and ultraviolet spectroscopy. The result shows that, all of the three compounds can quench the fluorescence of protein, and the process is static quenching which is caused by complex formation.