高等学校化学学报 ›› 2017, Vol. 38 ›› Issue (6): 1052-1058.doi: 10.7503/cjcu20160940

• 有机化学 • 上一篇    下一篇

氯化血红素催化氧化巯基形成二硫键

葛巍巍1,2, 陈静1, 宗良1, 李建1, 隋少卉1, 吴为辉1, 张鸣1, 董俊军1()   

  1. 1. 中国人民解放军防化学院, 北京 102205
    2. 公安消防部队高等专科学校, 昆明 650208
  • 收稿日期:2016-12-26 出版日期:2017-06-10 发布日期:2017-04-13
  • 作者简介:联系人简介: 董俊军, 男, 博士, 副教授, 主要从事多肽药物研究. E-mail: Dongjj536@sina.com
  • 基金资助:
    抗毒药物与毒理学国家重点实验室开放基金(批准号: PMC201507)和国民核生化灾害防护国家重点实验室开放基金(批准号: SKLNBC2013-01K)资助.

Efficient Oxidation of Thiols to Corresponding Disulfides Catalyzed by Hemin

GE Weiwei1,2, CHEN Jing1, ZONG Liang1, LI Jian1, SUI Shaohui1, WU Weihui1, ZHANG Ming1, DONG Junjun1,*()   

  1. 1. Institute of NBC Defence, Beijing 102205, China
    2. Public Security Fire Forces College, Kunming 650208, China
  • Received:2016-12-26 Online:2017-06-10 Published:2017-04-13
  • Contact: DONG Junjun E-mail:Dongjj536@sina.com
  • Supported by:
    Supported by the State Key Laboratory of Toxicology and Medical Countermeasures of China(No.PMC201507) and the State Key Laboratory of NBC Protection for Civilian, China(No.SKLNBC2013-01K).

摘要:

对氯化血红素催化氧化巯基形成二硫键的反应进行了研究, 发现N,N-二异丙基乙胺(DIEA)的加入可以提高氯化血红素的催化活性, 并降低其在氧化过程中的自聚现象. 在室温及少量DIEA存在下, 将氯化血红素和巯基乙酸甲酯按摩尔比1∶4 混合于pH=8.0的水溶液中, 敞口搅拌反应20 min, 可以催化空气氧化90%的巯基乙酸甲酯形成相应的分子间二硫键产物. 该催化氧化体系还可应用于多肽合成中, 在相同条件下, 只需2 h即可完成还原型催产素和利那洛肽的氧化环合, 生成高产率的催产素和利那洛肽环肽. 与传统的氧化方法相比, 氯化血红素催化氧化的方法具有高效、 环保的优点, 为多肽合成中二硫键的形成提供了一种新方法.

关键词: 氯化血红素, 氧化, 二硫键, 催产素, 利那洛肽

Abstract:

Hemin was used as a catalyst for the oxidation of thiols to corresponding disulfides. The addition of N,N-diisopropylethylamine(DIEA) can enhance the hemin catalytic activity and decrease the hemin self-oxidative degradation during the catalytic process. The methyl thioglycolate was quickly oxidized to corresponding disulfide product(completed 90% in 20 min) in the presence of 1/4 hemin in aqueous solution(pH=8.0) and DIEA involved in the reaction as an axial ligand. The oxidation was carried out at room temperature(ca. 20 ℃) under atmosphere condition. And this catalytic system was also successfully applied in disulfide bond formation in peptide synthesis. Oxytocin and linaclotide were used as model peptide. Compared with conventional oxidation reagents, the notable feature of this catalytic system is green and efficient, which provides an alternative way to formating disulfide bond in peptide synthesis.

Key words: Hemin, Oxidation, Disulfide, Oxytocin, Linaclotide

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