醋酸阿托西班制备工艺的研究

目的探讨醋酸阿托西班的固相合成工艺及纯化方法,以得到高纯度醋酸阿托西班。方法采用Fmoc氨基酸为原料,采用固相合成方法,以Rink-AM树脂为载体,TBTU/HOBt为缩合剂催化合成直链肽,以碘/乙醇液为氧化剂,采用固相环化,两个游离单巯基的氧化生成二硫键而得到目标环肽,体积比例为95/2.5/2.5裂解液TFA/EDT/Water裂解,制得阿托西班粗品,液相分析粗品的纯度为86.24%,制备反相高效液相色谱法纯化,制得醋酸阿托西班,纯度〉98%。结果合成醋酸阿托西班粗品,经制备反相高效液相色谱纯化,纯度〉98%。结论该方法简单,合成成本低,纯度高,可用于工业化生产。

Research on preparation technics of atosiban acetate

Objective To probe into solid-phase synthesis technics and purification method of atosiban acetate so as to obtain high purity of atosiban acetate. Methods Fmoc amino acid was selected as raw material.The Rink-AM resin as carrier and TBTU/HOBt as condensing agent,the linear peptide was catalyzed and synthesized by solid-phase synthesis.The solution of iodine/ethyl alcohol as oxidizing agent,the targeted cyclopeptide was obtained from disulfide bond generated from oxidation of two free single-thiols by solid-phase cyclization.The volume ratio was 95,2.5,and 2.5.The crude atosiban was obtained after cracking by lysis solution of TFA/EDT/water. The purity of crude atosiban was 86.24% by liquid phase analysis.The atosiban acetate was obtained by purification of reversed-phase high-performance liquid chromatography（RP-HPLC）,and the purity was over 98%. Results The synthesized crude atosiban acetate was purified by RP-HPLC,and its purity was over 98%. Conclusion At advantages of easy operation,low-cost synthesis,and high purity,it can be applied in industrial production.