3-Azidocoumarin Explained

3-Azidocoumarin is an organic compound that is used in the area of bioconjugation. It is a derivative of coumarin, a natural product and precursor for the widely used Coumadin. Azidocoumarin has emerged as a widely applicable labeling agent in diverse biological systems. In particular, it participates in the aptly named click reaction with alkynes.[1] Bioconjugation involves the labeling of certain cellular components and is applicable to fields such a proteomics and functional genomics with a detachable, fluorescent tag.[2]

Synthesis

A common way to produce the 3-azidocoumarin is by condensation of salicylaldehyde and N-acetylglycine or nitroacetate.[3] The intermediate is trapped with sodium azide to produce the 3-azidocoumarin. The isomeric 4-azidocoumarin (CAS# 42373-56-8) product can also be prepared from 4-hydroxycoumarin via the 4-chloro derivative, which reacts with sodium azide.[4]

Uses

This compound is used for bioconjugation. The target, which contains a terminal alkyne functional group, is treated with the organic azide in the presence of a Cu(I) catalyst. The resulting 1,2,3-triazole is fluorescent. The coumarin backbone is chosen to be used as the profluorophore due to its small size, biocompatibility, and its ability to be easily manipulated synthetically.[3] Illustrative of this is the labeling of biological compounds such as the protein calmodulin.[5] Neither the azidocoumarin nor the alkyne substrate fluoresce. Azidocoumarin is also inert in biological systems and insensitive to pH and solvent. A variety of azidocoumarin compounds have been evaluated.

Notes and References

  1. R. A. Evans . 2007 . The Rise of Azide–Alkyne 1,3-Dipolar 'Click' Cycloaddition and its Application to Polymer Science and Surface Modification . . 10.1071/CH06457 . 60 . 6 . 384.
  2. Hermanson, G. T. Bioconjugate Techniques; Academic Press: San Diego, 1996.
  3. Q. Wang . 2004 . A Fluorogenic 1,3-Dipolar Cycloaddition Reaction of 3-Azidocoumarins and Acetylenes . . 10.1021/ol047955x . 6 . 24 . 4603–4606. 15548086 . etal.
  4. W. Stadlbauer . 1986 . Methoden zur Darstellung von 4-Azido-2(1"H")-chinolonen [1] . Monatshefte für Chemie . 10.1007/BF00810876 . 117 . 11 . 1305–1323. 92478401 .
  5. T. Fekner . X. Li . M. M. Lee . M. K. Chan . amp . 2009 . A Pyrrolysine Analogue for Protein Click Chemistry . . 10.1002/anie.200805420 . 48 . 9 . 1633–1635 . 19156778.