Little Kevin N, Addai Gideon Ofosu, Stanwood Colin C, Bucag Christelle F T, Lin Xinsong, Chen Banghao, Whittington A Carl, Zhu Lei
Department of Chemistry and Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, Florida 32306-4390, United States.
Department of Biological Sciences, Florida State University, 319 Stadium Drive, Tallahassee, Florida 32306-4295, United States.
J Org Chem. 2025 Jun 20;90(24):8001-8012. doi: 10.1021/acs.joc.4c02920. Epub 2025 Jun 5.
We describe the effect of 1,4-diazabicyclo[2.2.2]octane (DABCO), a nucleophilic tertiary amine, in the synthesis of O-benzylcytosines in terms of both reaction efficiency and operational convenience. Benzylcytosines are substrates of the protein-labeling tool CLIP-tag. The applications of the synthesized CLIP-tag substrates in the fluorescent labeling of plasma membranes of live mammalian cells are demonstrated. For providing a fuller depiction of the function of DABCO in nucleophilic aromatic substitution (SAr) reactions involving nitrogen heterocycles, the efficiency and scope of DABCO-catalyzed substitutions on chlorinated pyrimidines are studied. The structures of single- and double-DABCO adducts of pyrimidine are characterized by single-crystal X-ray diffraction and NMR spectroscopy. The SAr reactivities of the DABCO adducts are assessed. Both the benefits and limitations of DABCO as a nucleophilic catalyst in SAr reactions are discussed.
我们从反应效率和操作便利性两方面描述了亲核叔胺1,4 - 二氮杂双环[2.2.2]辛烷（DABCO）在O - 苄基胞嘧啶合成中的作用。苄基胞嘧啶是蛋白质标记工具CLIP - tag的底物。展示了合成的CLIP - tag底物在活哺乳动物细胞质膜荧光标记中的应用。为了更全面地描述DABCO在涉及氮杂环的亲核芳香取代（SAr）反应中的功能，研究了DABCO催化的氯化嘧啶取代反应的效率和范围。通过单晶X射线衍射和核磁共振光谱对嘧啶的单DABCO加合物和双DABCO加合物的结构进行了表征。评估了DABCO加合物的SAr反应活性。讨论了DABCO作为SAr反应中亲核催化剂的优点和局限性。
