在原生化学结合过程中乙乙的内部激活
Yue Gui1, Lingqi Qiu1, Yaohao Li1
1State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University , 38 Xueyuan Road, Haidian District, Beijing 100191, China.
Journal of the American Chemical Society
|March 17, 2016
概括
这项研究引入了使用原生化学结合 (NCL) 的prolyl thioester合成的改进方法. 一个新的内部激活协议增强了这些具有挑战性的链接的反应性,使有效的键形成成为可能.
科学领域:
- 有机化学
- 生物化学
- 合成
背景情况:
- 与阿兰乙相比,在原生化学结合 (NCL) 中的反应性较低.
- 对于各种生物应用而言,有效合成含有的蛋白质至关重要.
研究的目的:
- 在NCL中开发一种温和高效的内部激活协议.
- 在联反应中克服prolyl thioester固有的低反应性.
主要方法:
- 在C端上引入4 - 墨替代剂,形成双循环酸中间体.
- 用传统方法比较反应速度的动力学研究.
- 机理研究以阐明结合路径.
主要成果:
- 在NCL中,4-mercaptoprolyl thioester方案显著增强了prolyl thioester的反应性.
- 发现反应速率与alanyl thioester相似.
- 结合过程通过类似NCL的途径进行,确保化学选择性和侧链兼容性.
- 建立了一个高效的单结合脱硫程序.
结论:
- 开发的协议提供了一种强大的合成含有prolyl thioester的的方法.
- 这种进步有助于高效地构建富含proline的序列,由Wilms瘤蛋白1的片段合成来证明.
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