Study On The Synthesis & Crystal Rotation Of Aztreonam

Aztreonam is the first clinical monocyclic β-lactam nucleus antibiotic which is different from other β-lactam antibiotics (such as penicillins, cephalosporins) in structure.1-position sulfonic acid group is part of the ring of the active β-lactam nucleus;β-lactamase have specific antibacterial spectrum and is stable for amino thiazole side chain at 3-position and methyl groups at 4-position.The demand of aztreonam increases rapidly for high safety. This dissertation makes studies about the synthetic process which contains important practical value.One step process based on literature was developed, which means that the active ester conducts acylation with small single ring, and then the resulting condensation product of tert-butyl ester aztreonam proceeds esterlysis reaction under concentrated hydrochloric acid and high temperature condition to obtain α-aztreonam. Herein, the synthetic process has been optimized so that the weight yield and quality of aztreonam has been improved, the weight yield is between 180～190%, HPLC content is more than 99.0%.Additionally, this article summaried the rotating crystal method from α-aztreonam to β-aztreonam. Three main ways to get the β-aztreonam from literature are as follows:1. β-aztreonam was dissolved in ethanol at 60℃, then precipitated β-aztreonam; 2.α-aztreonam was dissolved in ethanol with triethylamine, and then add hydrochloric acid ethanol solution to adjust pH to get β-aztreonam; 3. To finish crystal rotation with the mixture solution of acetone and ethanol. This article describes a new method, that is,α-aztreonam was dissolved in anhydrous ethanol, added hydrochloric acid ethanol solution at 13～17℃ to obtain β-aztreonam.The method described in this article was contrasted with the reported according to specified monograph of 2010 China Pharmacopeia, Volume Ⅱ, the results indicated that β-aztreonam obtained by the method described in this article was better.The β-aztreonam obtained has high purity, the structure of aztreonam is confirmed by 1H NMR & 13C NMR and Mass Spectrum. The synthetic route of aztreonam is started with cheap material that is easy to be obtained. The operation for rotation from α-aztreonam to β-aztreonam is simple, it is suitable for industrial manufacture.