Enamine–azide [2+3]-cycloaddition as a method to introduce functional groups into fluorescent dyes

• Published in: Tetrahedron letters 2019-01, Vol.60 (5), p.456-459
• Main Authors: Baleeva, Nadezhda S., Zaitseva, Snizhana O., Mineev, Konstantin S., Khavroshechkina, Anastasia V., Zagudaylova, Marina B., Baranov, Mikhail S.
• Format: Article
• Language: English
• Subjects: Azide; Cycloaddition; Enamine; Fluorophore
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2019.01.007

[Display omitted] •New approach to the functionalization of fluorescent dyes proposed.•The method are based on the use of the cycloaddition of “terminal” enamines to azides.•Only methyl group in the relevant place of dye molecule are needed for modification.•Fluorescent dyes from three different families were modified by the technique.•The modification does not reduce the fluorescence intensity but leads to a red-shift. Fluorescent dyes are a significant research tool with various applications in modern science. However, many experiments require the preparation of covalent dye conjugates, which is impossible without the presence of a functional group on the dye molecule. Unfortunately, the introduction of such groups is often a complicated task. Herein, we report a novel approach for the introduction of functional groups into fluorescent dyes, based on the [2+3]-cycloaddition reaction of “terminal” enamines with azides. The synthesis of such “terminal” enamines is carried out by the condensation of formamide acetals with a methyl group that is influenced by a strong electron withdrawing group. Thus, the proposed functionalization technique requires only the presence of a methyl group in the relevant position of the initial non-functionalized fluorescent dye.