EaStCHEM School of Chemistry, University of Edinburgh, Joseph Black Building, David Brewster Road, Edinburgh, EH9 3FJ, U.K.
Department of Chemistry, College of Science, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam 31441, Saudi Arabia.
Org Lett. 2023 May 5;25(17):3104-3108. doi: 10.1021/acs.orglett.3c00955. Epub 2023 Apr 21.
An efficient synthesis of -tetrazines by solid-phase methods is described. This synthesis route was compatible with different solid-phase resins and linkers and did not require metal catalysts or high temperatures. Monosubstituted tetrazines were routinely synthesized using thiol-promoted chemistry, using dichloromethane as a carbon source, while disubstituted unsymmetrical aryl or alkyl tetrazines were synthesized using readily available nitriles. This efficient approach enabled the synthesis of -tetrazines in high yields (70-94%), eliminating the classical solution-phase problems of mixtures of symmetrical and unsymmetrical tetrazines, with only a single final purification step required, and paves the way to the rapid synthesis of -tetrazines with various applications in bioorthogonal chemistry and beyond.
描述了一种通过固相方法合成 -四嗪的有效方法。该合成路线与不同的固相树脂和连接子兼容，并且不需要金属催化剂或高温。使用硫醇促进的化学方法，通常使用二氯甲烷作为碳源，合成单取代的四嗪，而使用易得的腈合成取代的不对称芳基或烷基四嗪。这种有效的方法能够以高产率（70-94%）合成 -四嗪，避免了经典的溶液相问题，即对称和不对称四嗪的混合物，仅需要单一的最终纯化步骤，为快速合成具有各种生物正交化学和其他应用的 -四嗪铺平了道路。
