醋酸阿托西班固相合成工艺的研究  

Study on solid phase synthetic process of atosiban acetate

作　　者：张利香 李新宇 张建松 钟祥龙 ZHANG Lixiang;LI Xinyu;ZHANG Jiansong;ZHONG Xianglong(R&D Center,Shenzhen Jianxiang Biopharmaceutical Co.,Ltd.,Shenzhen 518118,China;R&D Center,Shenzhen JYMed Technology Co.,Ltd.,Shenzhen 518118,China)

机构地区：[1]深圳市健翔生物制药有限公司研发中心,广东深圳518118 [2]深圳市健元医药科技有限公司研发中心,广东深圳518118

出　　处：《中国药物化学杂志》2025年第1期27-33,共7页Chinese Journal of Medicinal Chemistry

摘　　要：目的 优化醋酸阿托西班的制备工艺。方法 合成Fmoc-Pro-Orn-Gly-NH_(2)三肽后与树脂偶联,脱除保护基团后依次与醋酸阿托西班序列中相应的保护氨基酸或片段偶联,制得醋酸阿托西班线性肽树脂,经裂解、氧化后得到醋酸阿托西班。对上述路线的各项工艺参数进行优化,确定最优合成条件。结果与结论醋酸阿托西班总收率为64%,采用制备型反相高效液相色谱进行分离纯化后,醋酸阿托西班纯度为99%。该合成工艺便于偶联和裂解,有利于产品质量稳定,操作安全方便,产品质量可控,收率高,适合工业化生产。Atosiban acetate is one of the widely used drugs in clinical treatment of preterm birth.There are some deficiencies in the current synthetic process of atosiban acetate,which lead to the presence of some impurities in the product,such as isomers,inserted peptides,tBu cation capture impurities,and pro-deletion peptide impurities caused by steric hindrance and long reaction time.In this study,atosiban acetate was prepared by synthesizing Fmoc-Pro-Orn-Gly-NH_(2) tripeptide and then coupling amino acids or fragments in peptide sequence,which can reduce impurities in the product.In addition,the synthetic process of atosiban acetate was optimized,which was convenient for coupling and cleavage,and the operation was simple and safe.At the same time,the products prepared by this process have stable quality and high yield.Therefore,the process is suitable for the industrial production of atosiban aceteate.

关 键 词：醋酸阿托西班 多肽固相合成 工艺优化 

分 类 号：R914[医药卫生—药物化学]