普鲁卡因青霉素特定杂质的合成制备

目的 合成制备普鲁卡因青霉素的特定杂质2-(2-((4-((2-(二乙基氨基)乙氧基)羰基)苯基)氨基)-2-氧代-1-(2-苯基乙酰氨基)乙基)-5,5-二甲基噻唑烷-4-羧酸，该杂质为首次报道。方法 以青霉素G钾盐和盐酸普鲁卡因为原料，酸性条件下合成得到含有目标杂质的粗品，之后将该粗品固体通过反相制备色谱分离、冻干12h，得到该杂质的纯化样品。结果 得到纯化样品结构信息(质谱、核磁共振数据)与目标杂质相一致， 总收率2.5%，LC-MS纯度89.36%，HPLC纯度80.44%。结论 所得纯化样品为目标杂质2-(2-((4-((2-(二乙基氨基)乙氧基)羰基)苯基)氨基)-2-氧代-1-(2-苯基乙酰氨基)乙基)-5,5-二甲基噻唑烷-4-羧酸，可用于普鲁卡因青霉素产品的质量研究。

Synthesis and preparation of specific impuritiy of procaine penicillin#br#

Objective To synthesize and prepare the specific impurity of procaine penicillin 2-(2-((4-(2-(diethylamino)ethoxy))carbonyl)phenyl)amino)-2-oxo-1-(2-phenylacetamido)ethyl)-5,5- dimethylthiazolidine-4-carboxylic acid, and the impurity was reported for the first time. Methods The crude product containing the target impurity was synthesized using the penicillin G potassium salt and the procaine hydrochloride under the acidic condition of the raw material, and then the crude solid was separated by reverse phase preparative chromatography and lyophilized for 12 hours to obtain a purified sample of the impurity. Results Structural information (MS and NMR data) of the purified sample agreed with the target impurity, which was obtained with a total yield of 2.5%, LC-MS purity of 89.36%, and HPLC purity of 80.44%. Conclusion The purified sample was the target impurity, 2-(2-((4-(2-(diethylamino)ethoxy))carbonyl)phenyl)amino)-2-oxo-1-(2-phenylacetamido)ethyl)-5,5- dimethylthiazolidine-4-carboxylic acid, which could be used for the study on the quality of procaine