3-氨基-4-甲基-2-氧代氮杂环丁烷-1-磺酸的制备.doc

3-氨基-4-甲基-2-氧代氮杂环丁烷-1-磺酸的制备摘要氨曲南(Aztreonam)是第一个用于临床的单环β-内酰胺抗生素,该药对革兰氏阴性菌有很强的抗菌活性,对多种质粒介导和染色体介导的β-内酰胺酶有较高的稳定性。具有疗效高、耐受性好与青霉素和头孢菌素无交差过敏等特点。本品最早由施贵宝公司开发,临床用于治疗敏感细菌引起的感染。3-氨基-4-甲基-2-氧代氮杂环丁烷-1-磺酸(AQ-7)是制备氨曲南过程中一个重要的中间体,相关文献报道的合成方法很多但未必可行。我们选用L-苏氨酸为原料经过7步反应得到,并对其合成方法和反应条件进行了研究和改进。其中,L-苏氨酸甲酯盐酸盐的收率为91%;CBZ-苏氨酸甲酯的收率为85%;CBZ-苏氨酰胺的收率为80%;甲烷磺酰化反应的收率为82%;四丁基铵盐的制备收率为92%;关环反应收率为70%;氢化反应的收率为91%。关键词:氨曲南,中间体,收率ABSTRACTAztreonamisfirstusedintheclinicalsinglelinkbeta-lactanantibiotic,thismedicinehastheverystrongantibacterialactivenesstotheGram-negativebacteria,beta-lactamasewhichliesbetweenmanykindsofmaterialparticlesleadsandthechromosomeleadshasthehighstability,andhasthehighcurativeeffect,-amino-4-methyl-2-oxo-1-azetidinesulfonicacid(AQ-7)ispreparedasanimportantintermediateforaztreonam,-threonineastherawmaterialtopassthrough7stepsofresponses,,L-threoninemethylesteryieldingrateis91%;CBZ-threoninemethylesteryieldingrateis85%;CBZ-threonylamineyieldingrateis80%;Methanesulfurylresponseyieldingrateis82%;Tetrabutylammoniumsaltpreparationyieldingrateis92%;Cyclizationyieldingrateis70%;Thehydrogenationrespondedyieldingrateis91%.KeywordsAztreonam,intermediate,yieldingrate目录摘要……………………………………………………………………………………………ⅠABSTRACT……………………………………………………………………………………Ⅱ1绪论…………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………32氨曲南……………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………………