A Fluorogenic 1,3-Dipolar Cycloaddition Reaction of 3-Azidocoumarins and Acetylenes †

ArticleinOrganic Letters 6(24):4603-6 · December 2004with32 Reads
Impact Factor: 6.36 · DOI: 10.1021/ol047955x · Source: PubMed
Abstract

Copper(I)-catalyzed 1,3-dipolar cycloaddition reaction of nonfluorescent 3-azidocoumarins and terminal alkynes afforded intense fluorescent 1,2,3-triazole products. The mild condition of this reaction allowed us to construct a large library of pure fluorescent coumarin dyes. Since both azide and alkyne are quite inert to biological systems, this reaction has potential in bioconjugation and bioimaging applications. [reaction: see text]

    • "...and Fahrni [65], highly analogous to the azido-coumarin derivatives described by Sivakumar et al. [53]. However, clearly the reaction of a terminal alkyne with an azide requires the undesirable presence..."
      Other more recent fluorogenic azides, as developed by Shieh et al. [51] and Herner et al. [26] and even a fluorogenic azide substrate for generation of a near-infrared (NIR) triazole dye [52], are depicted in Fig. 8.Notwithstanding the elegancy and versatility of the azide-based fluorogenic probes, in particular to enable the visualization of biomolecules in living systems with biooorthogonal chemistry, it is also clear that for fluorescence detection of an azide label in a biomolecular environment, a complementary fluorogenic alkyne structure is desired. The earliest example of the latter (Fig. 9) was provided in the form of acetylenic derivatives of coumarin by Zhou and Fahrni [65], highly analogous to the azido-coumarin derivatives described by Sivakumar et al. [53]. However, clearly the reaction of a terminal alkyne with an azide requires the undesirable presence of copper(I) to induce the formation of triazole.
    [Show abstract] [Hide abstract] ABSTRACT: A nearly forgotten reaction discovered more than 60 years ago—the cycloaddition of a cyclic alkyne and an organic azide, leading to an aromatic triazole—enjoys a remarkable popularity. Originally discovered out of pure chemical curiosity, and dusted off early this century as an efficient and clean bioconjugation tool, the usefulness of cyclooctyne–azide cycloaddition is now adopted in a wide range of fields of chemical science and beyond. Its ease of operation, broad solvent compatibility, 100 % atom efficiency, and the high stability of the resulting triazole product, just to name a few aspects, have catapulted this so-called strain-promoted azide–alkyne cycloaddition (SPAAC) right into the top-shelf of the toolbox of chemical biologists, material scientists, biotechnologists, medicinal chemists, and more. In this chapter, a brief historic overview of cycloalkynes is provided first, along with the main synthetic strategies to prepare cycloalkynes and their chemical reactivities. Core aspects of the strain-promoted reaction of cycloalkynes with azides are covered, as well as tools to achieve further reaction acceleration by means of modulation of cycloalkyne structure, nature of azide, and choice of solvent.
    Full-text · Article · Apr 2016
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    • "...The compounds 2a and 2b were synthesized according to the reported method [49]. 3-Azido-7-hydroxycoumarin (2a). 1 H-NMR (300 MHz, MeOH-d 4 ): δ 7.40 (s, 1H). ..."
    [Show abstract] [Hide abstract] ABSTRACT: Peptoids, N-substituted glycine oligomers, are versatile peptidomimetics with diverse biomedical applications. However, strategies to the development of novel fluorescent peptoids as chemical sensors have not been extensively explored, yet. Here, we synthesized a novel peptoid-based fluorescent probe in which a coumarin moiety was incorporated via copper(I)-catalyzed azide-alkyne cycloaddition reaction. Fluorescence of the newly generated coumarin-peptoid was dramatically quenched upon coordination of the Cu(2+) ion, and the resulting peptoid-Cu(2+) complex exhibited significant Turn-ON fluorescence following the addition of CN(-). The rapid and reversible response, combined with cyanide selectivity of the synthesized peptoid, reflects a multistep photo-process and supports its utility as a new type of CN(-) sensor.
    Preview · Article · Mar 2016 · Molecules
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    • "...e probe in biological assays. The fluorogenic azide was prepared by the method of Sivakumar et al. [16] A 5 -modified thymidine would allow the combination of a nucleoside analog and a nitrogen mustard. ..."
      The obtained nitrogen mustard would be a good fluorophore probe in biological assays. The fluorogenic azide was prepared by the method of Sivakumar et al. [16] A 5 -modified thymidine would allow the combination of a nucleoside analog and a nitrogen mustard. This nucleoside analog might trigger an active transport through the cancer cell membranes.
    [Show abstract] [Hide abstract] ABSTRACT: This paper describes the synthesis of new click-generated nitrogen mustards and their biological evaluation. By using the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, we managed to synthesize eight new nitrogen mustards. This strategy paves the way for the synthesis of a new family of nitrogen mustard, with an important structural variability. Furthermore, we studied the biological activity of synthesized compounds by testing their cytotoxicity on four representative cancer cell lines A431, JURKAT, K562, and U266. One structure, 1-benzyl-4-(N,N-di-2-chloroethylaminomethyl)-1H-[11. Noll, D.M.; McG.Mason, T.; Miller, P.S. Formation and repair of interstrand cross-links in DNA. Chem. Rev. 2006, 106, 277–301.View all references,22. Rink, S.M.; Hopkins, P.B. Direct evidence for DNA intrastrand cross-linking by the nitrogen mustard mechlorethamine in synthetic oligonucleotides. Bioorg. Med. Chem. Lett. 1995, 5(23), 2845–2850.View all references,33. Chabner, B.A.; Collins, J.M. Cancer Chemotherapy: Principles and Practices, PA, J.B. Lippincott Company, Philadelphia, 1990, pp. 276–313.View all references]triazole, showed an interesting cytotoxic effect.
    Full-text · Article · Jul 2015 · Nucleosides Nucleotides & Nucleic Acids
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