头孢克肟及其关键中间体7-AVCA的合成工艺改进

摘要

目的 研究头孢克肟及其关键中间体7-AVCA的合成工艺,以酶解法替代传统化学裂解法.方法 经工艺考察及改进,最终确定以GCLE为起始原料,经关键中间体7-AVCA制备头孢克肟适合于生产的工艺.结果 所制得的头孢克肟质量好,总收率为64%.其中采用的酶解法工艺不仅解决了环保治理的瓶颈问题,同时改进工艺获得的中间体7-AVCA的质最明显优于其他方法,优质的7-AVCA从源头上起到提高下游原料药头孢克肟产品的含量及稳定性,降低杂质的作用.头孢克肟的结构经1H-NMR、IR和UV分析确证,色谱纯度经HPLC检测大于99%.结论 本文工艺与文献相比,操作简化,收率提高,产品质量优异,节能环保,适合于产业化.%Objective Synthetic process of cefixime and its key intermediate 7-Amino-3- ethenyl-8-oxo-5-thial-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (7-AVCA) was introduced.Enzymatic Hydrolysis was a substitute for Chemical Cleavage of Mismatch.Methods With studying and improving, the synthetic route was finalized as follows: Taking 4-methoxybenzy1-3-(chloromethyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4,2,0]oct2-ene-2-carboxylate (GCLE) as the starting material, the key intermediate 7-AVCA was synthesized by the step of enzyme hydrolysis.Results The target compound was obtained with total yield of 64％.Environmental problems was solved by the improved process and the high-quanlity 7-AVCA was of advantage to get the better cefixime with increasing contents, improving stability and low impurity level.The structure of cefixime was confirmed by 1H-NMR, IR and UV, and the HPLC purity was above 99％.Conclusion With the above process, Cefixime was synthesized with a simpler procedure and a higher yield comparing with the report in the literatures.The process of enzyme hydrolysis contributing to energy conservation and environment protection was suitable for the industrialization.