【摘要】 制备、分离并纯化了伏环孢素(1)的2个有关物质(A和B)，其中有关物质B为1的Z式异构体，即环[[(6Z)-(2S,3R,4R)-3-羟基-4-甲基-2-(甲基氨基)-6,8-壬二烯酰基]-L-2-氨基丁酰基-N-甲基-甘氨酰基-N-甲基-L-亮氨酰-L-缬氨酰-N-甲基-L-亮氨酰-L-丙氨酰-D-丙氨酰-N-甲基-L-亮氨酰-N-甲基-L-亮氨酰-N-甲基-L-缬氨酰]。首次报道在三乙胺/溴化锂体系下，将E式乙酰化伏环孢素(5)构型翻转并脱除乙酰基，可得到高纯度有关物质B。另外，在1的工艺优化过程中，首次发现并制备了过氧化杂质，即有关物质A，经高分辨质谱和核磁共振光谱分析，确证其结构为乙酰化环孢素A酸。上述2个化合物可对1原料药的质量控制提供一定的参考。更多还原

【Abstract】 Herein two related substances(A and B) of voclosporin(1) were prepared and purified.Compound B was Z-isomer of 1,named cyclo-[[(6Z)-(2S,3R,4R)-3-hydroxy-4-methyl-2-(methylamino)-6,8-nonadienoyl]-L-2-aminobutyryl-N-methyl-glycyl-N-methyl-L-leucyl-L-valyl-N-methyl-L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl].E configuration of acetylated voclosporin(5) was transferred into related substance B via configuration conversion and acetyl group removal under triethylamine/lithium bromide with high-purity,which was reported at the first time.In addition,in the process optimization of 1,the over-oxidized impurity,related substance A was found and prepared for the first time.Its structure was confirmed as acetylated cyclosporine A acid by high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy.The above two compounds can be served as the references for the quality control of 1.更多还原