Study On The Synthesis Of(3S,Trans)-3-Amino-4-Methyl-2-Oxo-1-Aze Tidine Sulfonic Acid

Aztreonam is the first clinic used drug of a new class of β-lactam antibiotics known as monobactam. 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 medicine was developed most early by the squibb company.It’s mainly clinical uses in the infection which caused by Aerobic Gram-negative bacteria and treats the sensitive bacterium, such as pneumonia, pleurisy, septicemia, especially for urinary tract infections.It’s cost is determined by its production costs of the main ring, at present, the synthesis method of the the aztreonam main ring at home and abroad have been reported in the literature, but there are few manufacturers at home, mainly rely on imports.In this paper we mainly synthesized the key intermediate of antibiotic aztr eonam,on the basis of other literature synthesis method, selection of L-threonine as initial material, through esterification with methanol, by amino protection wit h benzyl chloroformate, ammonolysis of ester with methanol solution of ammon ia, protection of hydroxyl groups with methane sulfonyl chloride. Using chloros ulfonic acid sulfonation reaction. Occurrence of cyclization reaction in alkaline c ondition.Then hydrogenation and deprotection of7step reaction, Finally get the aztreonam intermediates (3S, trans)-3-amino-4-methyl-2-oxo-l-azetidine sulfonic a cid, The reaction has high total yield. The synthesis conditions of each experi ment were optimized.The synthesis of intermediate products by1H-NMR and13C-NMR were th e target compounds, The final product of aztreonam in the small ring was verifl ed by HPLC and the purity is98.6%, to meet the requirements, the total yield was54.5%. Integrated per-experiment of reaction conditions, the process is easy to get raw materials, convenient operation, high yield, high product purity and t he reaction equipment requirements is not high. It is suitable for industrialized production.