摘要
以L-酪氨酸和琥珀酸酐为原料、氯化锂为催化剂、冰醋酸为反应溶剂合成了药品克拉维酸钾中的有关物质G。研究了反应溶剂的种类、反应物料配比、反应温度、反应时间等因素对有关物质G收率及纯度的影响,在L-酪氨酸和琥珀酸酐的摩尔比为1∶1.5、95℃加热反应1.0h的优化条件下,有关物质G粗品的最高纯度达到87.4%,收率为85.7%。通过制备液相色谱对粗品进行纯化,有关物质G的纯度达到99.6%,总收率为68.6%。采用LC-MS/MS对所合成物质进行了结构鉴定,确定其为欧洲药典中克拉维酸钾的有关物质G。
The related substance G in clavulanate potassium was synthesized from L-tyrosine and succinic anhydride in glacial acetic acid with lithium chloride as catalyst. Effects of type of reaction solvent, reactants ratio,reaction temperature and reaction time on the yield and purity of the related substance G were studied. Under the optimum conditions as follows：the molar ratio of L-tyrosine to succinic anhydride was 1 ： 1.5,the reaction temperature was 95 ℃, the reaction time was 1. 0 h,, the purity and yield of the related substance G reached 87.4% and 85.7 %, respectively. Preparative liquid chromatography was used for purification, while the purity reached 99.6 M and the total yield reached 68.6 %. The structure of the substance synthesized was proved to be the same as that of the related substance G in European Pharmacopoeia by LC-MS/MS.
出处
《化学与生物工程》
CAS
2013年第1期84-87,91,共5页
Chemistry & Bioengineering
关键词
克拉维酸
有关物质G
化学合成
结构鉴定
clavulanic acid
related substance G
chemical synthesis
structural identification
