摘要
目的合成左卡尼汀杂质A、杂质C和杂质D。方法以左卡尼汀为原料,脱水得到杂质A[(E)-4-(三甲基铵基)-2-烯-丁酸内盐];以(R)-环氧氯丙烷为原料,经胺解开环、氰基取代、盐酸水解反应得到杂质C盐酸盐[(2R)-N,N,N-三甲基-(4-氨基-4-氧代-2-羟基)-丁基铵氯化物];以杂质A为原料,制成甲酯、氨解得到杂质D [(E)-N,N,N-三甲基-(4-氨基-4-氧代-2-烯)-丁基铵]。结果设计合成3个杂质,含量均在95.0%以上。结论合成杂质纯度高,可用作左卡尼汀杂质研究对照品。
Objective To synthesize impurity A,impurity C and impurity D of levocarnitine.Methods( E)-4-( trimethylammonio) but-2-enoate( impurities A) was obtained from levocarnitine through dehydration.( 2 R)-4-amino-2-hydroxy-N,N,N-trimethyl-4-oxobutan-1-aminium chloride( impurities C hydrochloride) was obtained from( R)-eepichlorohydrin through open-loop by aminolysis,cyanyl substitution and hydrolysis of hydrochloric acid.( E)-4-amino-N,N,Ntrimethyl-4-oxobut-2-en-1-aminium( impurities D) was obtained from impurity A through forming methyl Ester and ammoniolysis.Results Three impurities were designed and synthesized. Their content were above 95. 0%. Conclusion Impurity A,impurity C and impurity D were of high purity and could be used as reference substance in the impurity research of Levocarnitine.
作者
任继波
于建华
刘印
高莹
杨学谦
REN Jibo;YU Jianhua;LIU Ying;GAO Ying;YANG Xueqian(Shandong Qidu Pharmaceutical Co.,Ltd.,Linzi 255400,China)
出处
《药学研究》
CAS
2020年第5期308-310,共3页
Journal of Pharmaceutical Research
关键词
左卡尼汀
促代谢药
杂质
合成
Levocarnitine
Metabolical drugs
Related substances
Synthesis
