The Research Of Two Kinds Of Optimization Of Synthesis Of β-lactam Antibiotic Side Chain Key Intermediates

β-lactam antibiotics are a kind of antibacterial activity,antibacterial spectrum,kidney dehydrogenase antibiotics,there are the world’s most widely used medical antibiotics.Cefixime and meropenem are all β-lactam antibiotics which are also a high proportion of the global market and an important drug.One of the key technologies for the synthesis of these two drugs is the synthesis of key side chain intermediates.Key side chain intermediates have a very important effect on the antibacterial activity,solubility,acidity and biocompatibility of β-lactam drugs.High-quality and efficient side-chain intermediates are essential for the development of β-lactam antibiotics.In this paper,the key intermediate side chains of cefacodime and meropenem were selected as the research object,and the synthetic route was developed and optimized.The thesis was divided into the following parts:The first chapter reviews the development of β-lactam antibiotics,the market overview,and the specific introduction to cefixime and meropenem.In the second chapter,the synthesis process of thiophene oxime side chain reactive thioester was studied,and the optimum reaction conditions were obtained.The results were discussed and analyzed.And the repeatability test was carried out according to the optimum reaction conditions.The stability and reproducibility of the experiment were verified.The total reaction yield of the whole synthesis process was37.0%.The purity of the obtained compound was above 99.5%,Single complex less than 0.15%.In the third chapter,the synthesis process of the side chain of meropenem was studied,and the suitable conditions for industrial production were obtained,and the reaction mechanism was discussed and analyzed.And the repeatability test was carried out according to the optimum reaction conditions.The stability and reproducibility of the experiment were verified.The total yield of the whole synthesis process was 58.3%,and the purity of the obtained compound was 98.6%.The fourth chapter characterizes the important intermediates in the synthesis process,including nuclear magnetic structure characterization,mass spectrometry,high performance liquid phase characterization and infrared spectroscopy.Chapter 5 summarizes the work done in this paper and the optimal reaction conditions.