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化学学报
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化学学报 ›› 1966, Vol. 32 ›› Issue (3): 261-275. 上一篇    下一篇

论文

带保护基的胰岛素A链羧端十二肽的合成

汪猷1, 徐杰诚1, 陈玲玲1, 李鸿绪1, 张伟君1, 李崇熙2, 陆德培2, 季爱雪2, 施溥涛2, 邢其毅2   

  1. 1. 中国科学院有机化学研究所;
    2. 北京大学化学系
  • 投稿日期:1966-03-15 发布日期:2013-06-03

SYNTHESIS OF A PROTECTED C-TERMINAL DODECAPEPTIDE OF THE A-CHAIN OF INSULIN

WANG YU1, HSU JE-ZEN1, CHEN LING-LING1, LI HONG-SHUEH1, CHANG WEI-CHUN1, LI CHUNG-HSI2, LOH TEH-PEI2, CHI AI-HSUEH2, SHI PU-TAO2, HSING CHI-YI2   

  1. 1. Institute of Organic Chemistry, Academia Sinica;
    2. Department of Chemistry, Peking University
  • Received:1966-03-15 Published:2013-06-03

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已知合成的胰岛素A链羧端带保护基的十二肽酯Ⅰ在不同条件下皂化,得十二肽Ⅱ,其物理性质略有差异,经制成牛胰岛素A链井进一步制成半合成牛胰岛素粗产物后,其生物活力相当于天然胰岛素的1—4%。根据二条不同的路线直接合成了带保护基的胰岛素A链羧端十二肽Ⅱ,路线一:由已知的四肽Ⅲ制成其酰肼衍生物,再转变为相应的迭氮化物后与脱N-苄氧羰基和γ-叔丁基的五肽Ⅴ(即Vb)缩合成九肽Ⅵ,Ⅵ经脱除N-保护基后与已知的三肽酰肼Ⅶ以迭氮化物法缩合郎得十二肽Ⅱ.路线二:三肽酰肼Ⅶ先制成迭氮化物再与脱N-保护基的已知二肽酯ⅩⅩⅢ反应成五肽酯ⅩⅩⅣ,再经肼解得五肽酰肼ⅩⅩⅤ,然后按迭氮化物法与脱苄氧羰基的二肽Ⅹ缩合成七肽酯ⅩⅩⅥ,再肼解得七肽酰肼ⅩⅩⅦ,最后通过迭氮化物法与五肽Vb缩合,亦得相同的十二肽Ⅱ.由这两种方法直接合成的十二肽Ⅱ,其质量较皂化所得为优,并已用于牛胰岛素A链的合成与结晶牛胰岛素的半合成和全合成。五肽Ⅴ和七肽ⅩⅩⅥ都曾各按二条不同的路线合成,而得到相同的产物,本文报导的合成肽段均经分析证明为化学纯的均一物质。

Dodecapeptide ester Ⅰ has been saponified to give a protected C-terminal dodeca-peptide (Ⅱ) of the A-Chain of insulin[1]. Further experiments showed that the saponification of ester Ⅰ under various conditions yielded preparations of dodecapeptide Ⅱ varying somewhat in melting points and solubility. These saponification products have been used for the partial synthesis of bovine insulin and all the crude hormone products obtained showed biological activity of 1-4% of natural insulin in mouse convulsion test. In order to avoid the saponification dodecapeptide Ⅱ has been directly synthesized by two alternative routes.