Study on the Synthetic Process of4-Acetoxy Azetidinone
|School||Hebei University of Science and Technology|
|Keywords||4-acetoxy azetidinone synthetic process benzamide enzymaticreduction chiral intermediates|
With the extensive use of antibiotics, bacterial resistance increases seriously. Carbapenems, as a group of new broad-spectrum β-lactam antibiotics, have an irreplaceable role in the clinical research because of its resistance for the vast majority of the β-lactamase, and the excellent efficacy for the treatment of a variety of bacterialinfections along with fewer side effects. So Carbapenems become a research hotspot in the development of anti-infective drugs. This topic is about the synthetic process of the4-acetoxy azetidinone (4-AA), which is a drug Intermediates of imipenem API belonging to the carbapenem antibiotic.The subject is carried out basing on the process of enzymatic reduction from India Arch and asymmetric synthesis from Japan Takasago. The benzamide as starting material is transformed into N-hydroxymethyl benzamide by hydroxymethyl reaction. And then4-AA is synthesized by condensation reaction with methyl acetoacetate, enzymatic reduction, deprotection, ester protection, purification with tartrate salt, protection reaction of hydroxy with t-butyl dimethyl chlorosilane, closed loop with a Grignard reagent and oxidation of peracetic acid.The overall yield of processes in above is more than18%, and the purity of product is greater than98.2%, the content of4-AA is higher than96.7%.The enzymatic reduction is applied in the synthesis of4-AA as chiral intermediates in the subject. It provides basic data and new research directions for the synthetic research of4-AA subsequently. This topic also includes partial improvements of synthesis from the literature. For example, it reduces the step of adjusting the pH with triethylamine and the concentration of peracetic acid in the peroxidation. The results provide basis for the industrial production of4-AA, and in a certain extent, the dangers inherent from industrial production are also reduced.