Research On Optimization Of Process Of Hypolipidemic Drug Ezetimibe And Antithrombotic Drug Warfarin

With the development of society and excessive intake of cholesterol, hyperlipidemia has been a growing threat to human beings. Morbidity statistics has shown the increasing number of people is suffering from cardiovascular disease like coronary heart disease, atherosclerosis and etc. Moreover, a higher rate of younger patients come into appear. Ezetimibe, an effective cholesterol inhibitor which acts by decreasing cholesterol absorption in the small intestine, has been applied in clinical alone or together with statins.Thrombus diseases have been one of the most threatening cardiovascular diseases as heart attack and stroke keeps ranking top of death toll. Currently, warfarin is one of the effective antithrombotic drugs in use.The research on ezetimibe and warfarin is of great significance in both academic field and industrial application. This work analyzed the existing synthesis methods for ezetimibe and warfarin. With fluorobenzene, glutaric anhydride, p-hydroxyl benzaldehyde and p-fluoro aniline as raw material, the low cost process involved F-C acylation. chiral reduction of hydroxyl, condensation, protection of hydroxyl group, nucleophilic addition, cyclization and deprotection to afford ezetimibe with the yield of 26.1%. Additionally, the key catalyst for chiral reduction of hydroxyl was also prepared.The first part of this paper introduces the current progress of hypolipidemic drugs, describes the pharmacological study of the cholesterol inhibitor Ezetimibe and the production standardsofEzetimibe sheet in detail, discusses the synthesis method of Ezetimibe, introduce multiple synthesis route, analyze and choose reasonable and low cost route, and then make the further optimization on the basis of the experience, synthesisaAn important chiral catalyst of hydroxyl reduction named Me-CBS catalyst.The second part introduces the research progress of antithrombotic drugs, and introduces the synthetic process of Warfarin,makes up better conditions of the each reaction, and studies the one-pot synthetic route of warfarin. The final product was obtained by Claisen-Schmidt condensation, Aldol Reactionl, and Michael addition..