de Geus Mark A R, Groenewold G J Mirjam, Maurits Elmer, Araman Can, van Kasteren Sander I
Leiden Institute of Chemistry, The Institute for Chemical Immunology, Leiden University Einsteinweg 55 2333 CC Leiden The Netherlands
Chem Sci. 2020 Sep 8;11(37):10175-10179. doi: 10.1039/d0sc03216f.
The inverse electron-demand Diels-Alder (IEDDA) pyridazine elimination is one of the key bioorthogonal bond-breaking reactions. In this reaction -cyclooctene (TCO) serves as a tetrazine responsive caging moiety for amines, carboxylic acids and alcohols. One issue to date has been the lack of synthetic methods towards TCO ethers from functionalized (aliphatic) alcohols, thereby restricting bioorthogonal utilization. Two novel reagents were developed to enable controlled formation of -cyclooctene (CCO) ethers, followed by optimized photochemical isomerization to obtain TCO ethers. The method was exemplified by the controlled bioorthogonal activation of the operon system in using a TCO-ether-modified carbohydrate inducer.
逆电子需求狄尔斯-阿尔德（IEDDA）哒嗪消除反应是关键的生物正交断键反应之一。在该反应中，反式环辛烯（TCO）作为用于胺、羧酸和醇的四嗪响应性笼蔽部分。迄今为止的一个问题是缺乏从功能化（脂肪族）醇合成TCO醚的方法，从而限制了生物正交应用。开发了两种新型试剂，以实现反式环辛烯（CCO）醚的可控形成，随后通过优化的光化学异构化获得TCO醚。该方法通过使用TCO-醚修饰的碳水化合物诱导剂对大肠杆菌中的操纵子系统进行可控生物正交激活得到了例证。
