Study On The Synthesis Of Key Intermediate 4 - AA Of Carbapenem And Penicillin Antibiotics

The synthetic process of a key intermediate for synthesis of carbapenem and penem antibiotics, (1’R,3R,4R)-4-acetoxy-3-[(1’-t-butyldimethylsilyloxy)ethyl]-2-azetidinone (4-AA), is studied in this paper.The classification and development ofβ-lactam antibiotics is introduced briefly in this paper, the research progress of carbapenem and penem compounds and the importance of 4-AA as a key of carbapenem as well as penem antibiotics are introduced respectively. The synthesis process of 4-AA is mainly discussed. Several synthetic routes reported of 4-AA are compared and investigated, finally L-threonine is used as starting material and the target compound is prepared via diazotization、chlorination、N-alkylation、acylation、cyclization、hydroxyl protection、N-deprotectio、Baeyer-Villiger oxidation、transesterification nine steps, in overall yield of 14.2%.Most of the reactions involved are mild and easily put in practice and have little environmental pollution, so this process has an economic advantage in view of the application for large-scale production.The structures of the intermediates and final compound were confirmed by 1H-NMR, 13C-NMR, MS and IR.