A Mild Aqueous Sonogashira Reaction as a Fluorescent Labeling Strategy for 5-Bromide-2′-Deoxyuridine

Molecules

Yongxin Gao¹  Shigang Shen²  Hui Wen³  Shufang Wang³  Huaqing Cui³ 

[1] Beijing Key Laboratory of Active Substances Discovery and Drugability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China;Key Lab of Analytical Science and Technology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071000, China;State Key Laboratory of Bioactive Substances and Function of Natural Medicine, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China;

关键词: Sonogashira reaction;    BrdU;    aqueous reaction;    fluorescent labeling;   

DOI  :  10.3390/molecules23010154

来源: DOAJ

【 摘 要 】

C5-modified uridines are a valuable class of nucleoside analogues, both as potent chemotherapy agents and through their use as the conjunction site in DNA labeling strategies. As an important C5-modified uridine, BrdU has been used in cell proliferation assays since the 1980s. Currently, the detection of BrdU relies on traditional immunostaining; however, this approach has its limitations. Thus, it is desirable, albeit difficult, to develop chemistry methods to fluorescently label BrdU in a cellular context. In the present study, we report our efforts toward developing a robust chemistry methodology for BrdU fluorescent labeling. The Sonogashira reaction was chosen as the key reaction, and various alkynyl groups (aliphatic or aryl) containing fluorescent dyes were synthesized to cross-couple with BrdU. Various bases and catalyst systems were screened to evaluate the optimum conditions. A mild aqueous Sonogashira reaction (K2PdCl4, S-Phos, n-Bu4N+OH−, Sodium d-isoascorbate, EtOH/H2O = 1:1, 37 °C, Ar) was obtained to enable high-yielding BrdU fluorescent labeling.

【 授权许可】

Unknown