化工学报 ›› 2012, Vol. 63 ›› Issue (4): 1189-1194.DOI: 10.3969/j.issn.0438-1157.2012.04.028

• 生物化学工程与技术 • 上一篇    下一篇

罗红霉素相关物的制备

李玲莉1,聂乙娇2,刘聪2,姚国伟2,孙立权2   

  1. 1北京理工大学化工与环境学院,北京100081;2北京理工大学生命学院,北京100081
  • 收稿日期:2011-07-14 修回日期:2011-12-28 出版日期:2012-04-05 发布日期:2012-04-05
  • 通讯作者: 孙立权

Preparation of roxithromycin related substances

LI Lingli1,NIE Yijiao2,LIU Cong2,YAO Guowei2,SUN Liquan2   

  1. 1School of Chemical Engineering and Environment, Beijing Institute of Technology, Beijing 100081, China; 2School of Life Science, Beijing Institute of Technology, Beijing 100081, China
  • Received:2011-07-14 Revised:2011-12-28 Online:2012-04-05 Published:2012-04-05

关键词: 红霉素A 9-(E)肟, 罗红霉素, 罗红霉素Z, N-去甲基罗红霉素, 去克拉定糖罗红霉素

Abstract: N-Demethyl roxithromycin, 3-decladinosyl roxithromycin and roxithromycin Z are specified related substances to be controlled in European Pharmacopoeia 7.0, which are derived from roxithromycin. These compounds are required for its routine assay, however cannot be commercially available in China.The related substances were synthesized according to a new procedure developed from previous methods.In the producing process, erythromycin A 9-(Z)-oxime was produced from erythromycin A 9-(E)-oxime in the presence of a strong base.Roxithromycin Z was synthesized by the reaction between erythromycin A 9-(Z)-oxime and methoxyethoxy methyl chloride ether in ethyl acetate at a low temperature, such as lower than 5℃.Roxithromycin Z was then separated with silica chromatography and purified by semi-preparative HPLC.N-Demethyl roxithromycin was prepared by N-demethylation of roxithromycin with iodine and sodium acetate in aqueous solution of sodium hydroxide(pH=8—9), and was purified by two-stage recrystallization.And 3-decladinosyl roxithromycin was obtained through a process of acidic hydrolysis catalyzed by aqueous hydrochloride at room temperature, and was also purified by silica chromatography and semi-preparative HPLC.All three compounds, N-demethyl roxithromycin, 3-decladinosyl roxithromycin and roxithromycin Z were determined by HPLC to high purity of over 95%.Their structures were identified by MS,1H NMR and 13C NMR.In this paper, three producing routes of the compounds have been established successfully.The obtained compounds would provide a new standard reference of roxithromycin for drug assay in Chinese Pharmacopieia.

Key words: erythromycin A 9-oxime, roxithromycin, roxithromycin Z, N-demethyl roxithromycin, 3-decladinosyl roxithromycin

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