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有机化学
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有机化学 ›› 2010, Vol. 30 ›› Issue (06): 837-842. 上一篇    下一篇

研究论文

片段缩合法合成亮丙瑞林

岑涛1，周成1，武秀明1，姜波1，祝社民2，沈树宝*,1   

  1. (1南京工业大学生物与制药工程学院 材料化学工程国家重点实验室 南京 210009)
    (2南京工业大学材料科学与工程学院 材料化学工程国家重点实验室 南京 210009)
  • 收稿日期:2009-08-17 修回日期:2009-11-26 发布日期:2010-01-08
  • 通讯作者: 沈树宝 E-mail:zsbshen@njut.edu.cn,zsbshen@126.com
  • 基金资助:

    国家863资助项目(No.2009AA05Z313)；国家863资助项目(No.2006AA02Z211)；国家自然科学基金资助项目(50872052)；国家自然科学基金资助项目(20376034)；江苏省自然科学基金资助项目(BK2006181)；江苏省高校研究生创新

Synthesis of Leuprorelin Using Segment Condensation Approach

Cen Tao1 Zhou Cheng1 Wu Xiuming1 Jiang Bo1 Zhu Shemin2 Shen Shubao*,1   

  1. (1 State Key Laboratory of Materials-Oriented Chemical Engineering, College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing 210009)
    (2 State Key Laboratory of Materials-Oriented Chemical Engineering, College of Material Science and Engineering, Nanjing University of Technology, Nanjing 210009)
  • Received:2009-08-17 Revised:2009-11-26 Published:2010-01-08

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被引次数

5 | 2

将亮氨酸作为C末端氨基酸, 采用片段缩合策略(2＋7)合成亮丙瑞林. 液相法合成困难序列Fmoc-Arg(Pbf)- Pro-NHEt时, 以DIC为缩合试剂, THF作为溶剂, Pro-NHEt•HCl与Fmoc-Arg(Pbf)-OH的物质的量比为1∶1.25, 产率可达84.8%. 采用固相法合成的全保护七肽片段产率为81.3%. 全保护的七肽片段与Arg(Pbf)-Pro-NHEt在液相中缩合时, 以DMF∶DMSO (V∶V＝1∶1)为溶剂, HATU/HOBt/DIEA为缩合剂, 得全保护的九肽. 切割侧链后得到目标产物亮丙瑞林.

关键词: 片段缩合法, 亮丙瑞林, 多肽合成, 困难序列

Leuprorelin was synthesized by segment condensation strategy (2＋7). The protected dipeptide, Fmoc-Arg(Pbf)-Pro-NHEt, was synthesized in solution phase and its yield reached 84.8%, when DIC was used as the coupling reagent, THF as the solvent, and the molar ratio of Pro-NHEt•HCl and Fmoc-Arg(Pbf)-OH was 1∶1.25. The protected pentapeptide synthesized in solid phase yielded 81.3%. The protected leuprorelin was synthesized by segment condensation using DMF∶DMSO (V∶V＝1∶1) as the solvent and HATU/HOBt/DIEA as the coupling reagent. The target product of leuprorelin was achieved after cutting the side-chain.

Key words: segment condensation, leuprorelin, peptide synthesis, difficult sequence