以Rink Amide MBHA 树脂为载体，Fmoc 保护的氨基酸为原料，HOBt、DIC 为缩合试剂，按照加尼瑞克的氨基酸序列进行固相合成得到加尼瑞克粗肽；经2 步反相高效液相色谱法进行分离纯化，得到纯度大于99％的加尼瑞克纯品，总收率达31.03％；最后对产品中的醋酸含量进行控制，经过冻干得到了纯度大于99％的醋酸加尼瑞克样品；讨论了醋酸加尼瑞克制备工艺过程中的关键因素，并对工艺条件进行了优化。
Abstract
The crude peptide of ganirelix was successfully synthesized according to its amino acid sequence by using Rink Amide MBHA resin as a solid support, Fmoc-amino acids as raw materials and HOBt/DIC as coupling reagents. The purity of final ganirelix is over 99％ after isolated and purified using two-step reversed-phase high performance liquid chromatography(HPLC)method, and the total yield was 31.03％. Finally, the standard API was abtained via freeze-dried and the acetic acid content was controlled. Also, the impact factors on the process was discussed.
关键词
醋酸加尼瑞克 /
固相合成 /
制备工艺 /
促性腺激素释放激素(GnRH)受体拮抗药
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Key words
ganirelix acetate /
solid-phase synthesis /
preparation technology /
gonadotropin-releasing hormone receptor antagonist
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参考文献
[1] Nestor Jr JJ, Vickery BH. Nonapeptide and decapeptide analogs of LHRH useful as LHRH antagonists: US, 4801577 [P]. 1989-01-31.
[2] Nestor Jr JJ, Mcclure NL. Temporary minimal protection synthesis of serine-containing polypeptides: US, 5212288 [P]. 1993-05-18.
[3] 杨桂英, 东圆珍, 冯 军, 等. 兰瑞肽的制备[J]. 中国医药工业杂志, 2013, 44(10): 961—965.
[4] Sarin VK, Kent SB, Tam JP, et al. Quantitative monitoring of solid-phase peptide synthesis by the ninhydrin reaction [J]. Anal Biochem, 1981, 117(1): 147—157.
[5] 王德心. 固相有机合成原理及应用指南[M] . 北京: 化学工业出版社, 2004.
[6] Product information. Orgalutran PI A140925 v5 (CCDSMK8761- INJ-052012)[S]. 2014-09-25.
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脚注
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