阿维莫泮非对映异构体的合成与表征

Synthesis and characterization of the diastereoisomer of Alvimopan

以(αR,3R,4R)-4-(3-羟基苯基)-3, 4-二甲基-2-(苯基甲基)-1-哌啶丙酸甲酯为起始原料,经水解、缩合、水解三步反应得到阿维莫泮非对映异构体杂质[[2R)-[[4(R)-(3-羟基苯基)-3(R), 4-二甲基-1-哌啶基]甲基]-1-氧代-3-苯基丙基]氨基]乙酸。经NMR、IR、MS和HPLC对合成产物的结构及纯度进行了表征,确证为目标化合物,纯度达98.0%以上,可作为阿维莫泮药物质量控制的杂质对照品。

The diastereroisomer of Alvimopan, named [[2(R)-[[4(R)-(3-hydroxyphenyl)-3(R), 4-dimethyl-1-piperidine]methyl]-1-oxo-3-phenyl propionic acid, was synthesized via three step reactions using(αR, 3R, 4R)-4-(3-hydroxyphenyl)-3, 4-dimethyl-2-(phenylmethyl)-1-piperidine propionate as starting material. The structure of the target compound was confirmed by NMR, IR and MS, with the purity was tested by HPLC to be more than 98%, which means the synthesized diastereroisomer can be used as the reference substances of the impurities in the quality control of alvimopan.