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 ABSTRACT Aztreonam is first used in the clinical single link beta - lactan antibiotic, this medicine has the very strong antibacterial activeness to the Gram-negative bacteria, beta - lactamase which lies between many kinds of material particles leads and the chromosome leads has the high stability, and has the high curative effect, the tolerance is good with the penicillin and the cephalosporin does not have reports on accomplishments characteristic and so on allergy. This was developed most early by the squibb company for clinical uses in the infection which treats the sensitive bacterium. 3- amino -4- methyl -2- oxo-1-azetidinesulfonic acid (AQ-7) is prepared as an important intermediate for aztreonam, the related literatures reporte many synthetic method but are not necessarily feasible. We select L- threonine as the raw material to pass through 7 steps of responses , and have conducted the research and the improvement to its synthetic method and the response condition. Among them, L- threonine methyl ester yielding rate is 91%; CBZ- threonine methyl ester yielding rate is 85%; CBZ- threonyl amine yielding rate is 80%; Methane sulfuryl response yielding rate is 82%; Tetrabutyl ammonium salt preparation yielding rate is 92%; Cyclization yielding rate is 70%; The hydrogenation responded yielding rate is 91%. Keywords Aztreonam, intermediate，yielding rate 目 录 摘 要……………………………………………………………………………………………Ⅰ ABSTRACT…………………………………………………………………………………… Ⅱ 1 绪论……………………………………………………………………………………………1 1.1 课题背景……………………………………………………………………………………