An inexpensive fluorescent labeling protocol for bioactive natural products utilizing Cu(I)-catalyzed Huisgen reaction

Labeling of bioactive small molecules with organic dyes for various applications in cell biology has been emerging as an attractive research field. Using an easily prepared and inexpensive fluorescein derivative 1 and a Cu(I)-catalyzed Huisgen reaction, an efficient fluorescent labeling strategy is developed generally for bioactive natural products. Essentials of a successful labeling include the personalized introduction of an azido functionality to specific targets by a selective and efficient manner, and the strategic adjustment of reaction sequence to avoid possible side reactions under the 'click' reaction conditions. Such a protocol has been successfully applied to the fluorescent labeling of four bioactive small molecules in different chemical categories in this study. Advantages of this labeling protocol include the use of inexpensive reagents, ease of operation, free-of-protections at the 'click' step, and suiting a wide range of bioactive molecules bearing the reactive functionalities.