文献类型：期刊文献

中文题名：抗高血压新药奥美沙坦的合成

英文题名：Synthesis of a Novel Angiotensin Ⅱ Receptor Antagonist Olmesartan Medoxomil

作者：虞心红[1];汤建[1];温新民[1];毛庆华[1];沈永嘉[1]

机构：[1]华东理工大学化学与制药学院,上海200237

年份：2005

卷号：31

期号：2

起止页码：189

中文期刊名：华东理工大学学报（自然科学版）

外文期刊名：Journal of East China University of Science and Technology

收录：CSTPCD;;Scopus;北大核心:【北大核心2004】；CSCD:【CSCD2011_2012】；

语种：中文

中文关键词：奥美沙坦;抗高血压药;血管紧张素Ⅱ受体阻断剂;合成

外文关键词：olmesartan medoxomil;antihypertensive agent;angiotensin Ⅱ receptor blockers;synthesis

摘要：以酒石酸为起始原料,经硝化、环合、酯化、格利雅反应、N-烃化、水解、O-烃化、水解去保护等反应制得奥美沙坦,总收率32.7%。目标化合物及各关键中间体的结构均经MS,1H-NMR,IR分析确证,并对反应条件进行了改进。2-丙基咪唑二羧酸(2)采用酒石酸用混酸硝化后与醛氨溶液缩合制得,避免了文献中所用有毒的2,3-二氨基丁烯二腈。N-烃化以价廉易得的氢氧化钾代替叔丁醇钾、氢化钠。在水解反应中以氢氧化钠代替氢氧化锂,反应时间由20h缩短为2h。O-烃化以丙酮代替二甲基乙酰胺作溶剂,后处理更加简便。整条合成路线条件温和、操作简单、成本低廉,较适合于工业化生产。
In this paper, a new angiotensin Ⅱ receptor antagonist, (5-methyl-2-oxo-1,3-dioxol-4-yl)　methyl-4-(1-hydroxy-1-methylethyl)-2-propyl-1-[(2′-1H-tetrazol-5-yl-biphenyl-4-yl) methyl] imdazole-5-carboxylate(Olmesartan medoxomil), was synthesized using tartaric acid as starting material via nitration, cyclization, esterifcation, Grignard reaction, N-alkylation, hydrolyzation, O-alkylation and N-deprotection in 32.7% overall yield. The structure of title compound has been characterized by MS(mass spectrum), (()~1H)-NMR (nuclear magnetic resonance) and IR (ifrared spectrum). The condensation of 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylic acid ethyl ester with 5-[4′-(bromomethyl) biphenyl-2-yl]-1-(triphenylmethyl) tetrazole by means of potassium hydroxide in DMF, instead of potassium tert-butoxide in dimethylacetamide or sodium hydroxide in DMF, gives the corresponding N-alkylated product, which is hydrolyzed with sodium hydroxide, instead of lithium hydroxide, in dioxane-water to the desired acid. The improved process is more practical.