Studies On The Synthesis And Purification Of Two Antimicrobial Drugs: Aspoxicillin And Luteolin

Aspoxicillin and luteolin are two drugs and both of them exhibit strong antimicrobial activity. Aspoxicillin belongs to wild spectrum penicillin while luteolin is a kind of flavonoids. Both of them got some problems in preparing and application: Aspoxicillin has neither been produced nor applied in domestic. The research and application of luteolin has been limited by the low content in nature. In that case, the study on the synthesis and purification of aspoxicillin and luteolin is required.In this thesis, aspoxicillin has been synthesized with new method, using two different NH2 protecting groups. The mechanism of preparing activable ester has been discussed. We also synthesized luteolin from rutin with the assistance of microwave and study the solid-liquid equilibrium of the reactant and the product.The main content of this thesis is as following:In the first chapter of this thesis, we summarize the references about our research and introduce the correlated research background. The current developments were summarized and the research contents of this thesis were described.In the second chapter, aspoxicillin, a new kind of semi-synthetic penicillin, was successfully synthesized during 5 steps using tert-butyl ester (BOC) and benzyl ester (Cbz) as NH2 protecting group. Most of the intermediate products and end product were obtained and confirmed by MS and NMR.In the third chapter, the mechanism of preparing the active ester of N-hydroxysuccinimide during the synthesis of aspoxicillin was studied by B3LYP method at the level of 6-31G(d). The geometric configurations of reactants, products, intermediates, and transition states in the reaction have been optimized and vibrational analysis has been performed. The single-point was calculated and the activation energy of the reactions has been discussed. Relatively low temperature, low concentration of EDC-HCl and a long-term reaction are favorable for the preparation of the products, which is.essentially consistent with the experimental results.In the forth chapter, luteolin was synthesized from rutin with the assistance of microwave. To optimize the process for the purification of the synthetic product, the solid-liquid equilibrium of rutin and luteolin was studied by analytical method. Simple procedure to analyze rutin and luteolin with high performance liquid chromatography (HPLC) method was set up, respectively. The solubilities of rutin and luteolin in some commonly used solvents and ethanol+water mixed solvents were determined using HPLC at different temperatures.In the fifth chapter, a three-parameter equation was used to correlate the experimental data of the solubilities of rutin and luteolin in different solvent systems and showed satisfactory results. An appropriate method of luteolin purification was given.In the last chapter, all of the experiment work was summarized. We find the deficiencies in the work and propose the idea of the latter research.