Lin Fiona L, Hoyt Helen M, van Halbeek Herman, Bergman Robert G, Bertozzi Carolyn R
Department of Chemistry, Howard Hughes Medical Institute, University of California, and Materials Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
J Am Chem Soc. 2005 Mar 2;127(8):2686-95. doi: 10.1021/ja044461m.
The Staudinger ligation of azides and phosphines has found widespread use in the field of chemical biology, but the mechanism of the transformation has not been characterized in detail. In this work, we undertook a mechanistic study of the Staudinger ligation with a focus on factors that affect reaction kinetics and on the identification of intermediates. The Staudinger ligation with alkyl azides was second-order overall and proceeded more rapidly in polar, protic solvents. Hammett analyses demonstrated that electron-donating substituents on the phosphine accelerate the overall reaction. The electronic and steric properties of the ester had no significant impact on the overall rate but did affect product ratios. Finally, the structure of an intermediate that accumulates under anhydrous conditions was identified. These findings establish a platform for optimizing the Staudinger ligation for expanded use in biological applications.
叠氮化物与膦的施陶丁格连接反应在化学生物学领域已得到广泛应用，但其转化机制尚未得到详细表征。在这项工作中，我们对施陶丁格连接反应进行了机理研究，重点关注影响反应动力学的因素以及中间体的鉴定。与烷基叠氮化物的施陶丁格连接反应总体上是二级反应，在极性质子溶剂中进行得更快。哈米特分析表明，膦上的供电子取代基会加速整个反应。酯的电子和空间性质对总反应速率没有显著影响，但会影响产物比例。最后，确定了在无水条件下积累的中间体的结构。这些发现为优化施陶丁格连接反应以扩大其在生物应用中的用途奠定了基础。
Zotero 插件