Enamine - smart chemistry solutions
PRODUCTS


Azides for Click Chemistry

Recently, a set of synthetic protocols termed as “Click Chemistry” have attracted enormous attention in medicinal chemistry and related areas of research. The concept was originally introduced by H. C. Kolb, M. G. Finn and K. B. Shaprless at The Scripps Research Institute [1]. The main idea behind the “click Chemistry” is the use of mild, highly reliable, selective and powerful reactions for the rapid synthesis of large arrays of chemical compounds. In medicinal chemistry, this approach allows fast synthesis of combinatorial libraries for biological screening at low cost and with high efficiency.

Not many chemical reactions meet the stringent criteria to be selected for use in this emerging area. The reactions must be modular, wide in scope, proceed with high yields, stereospecific and biocompatible. Simple reaction conditions and simple isolation protocols are also of paramount importance. These criteria ensure generating substances quickly and reliably by joining together small reactive units, or building blocks. The biocompatibility opens the prospectives of in vivo reactions.

Among the reactions conforming to Click Chemistry requirements, three classes were identified: a) nucleophilic opening of strained electrophiles, for example, aziridines or epoxides; b) condensation reactions of aldehydes or ketones, for instance, formation of hydrazones and oximes; c) cycloaddition reactions.

One of the most useful is the reaction between organic azides and alkynes, calalysed by Cu(I) compounds. This reaction is a [3+2] cycloaddition [2], [3] which is highly specific, can be carried out in water, and fully bioorthogonal [4], [5]. As a result, it has rapidly established a prominent role in materials science [6], [7], medicinal [8], and bioconjugation chemistry [8], [9].

In the search for new drugs, the Click Chemistry started to give very promising results. For example, the very potent inhibitors 1-3 of various enzymes were discovered by the fragment approach made possible by the use of the appropriate linkers (highlighted in red), constructed by [3+2] azide-alkyne cycloaddition [10].

12
3


Understanding the importance of the fast access to the diverse building blocks used in Click Chemistry, Enamine offers several collections of compounds providing access to many classes of organic fragments – heterocyclic rings, aromatic, heteroaromatic, aliphatic residues, functionalized by different functional groups. Recently we released set of Hydrazine Building Blocks suitable for Click Chemistry reactions. In this issue, we introduce the collection of azides, available from Enamine upon request, due to a limited shell life of these highly reactive compounds. Reliability of this offer is backed up by our vast experience in preparation of various fine chemicals and particularly azides. Examples of the most interesting azides available from Enamine are shown below. The complete database of azides offered by Enamine (including also acyl and sulfonyl azides) can be downloaded here.

 

EN400-16306 EN400-16304 EN400-16301
EN400-16258 EN400-16257 EN400-16254
EN400-16131 EN400-16129 EN400-16126

 

1. H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem. Int. Ed. 2001, 40, 2004 – 2021.

2. V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew. Chem. Int. Ed. 2002, 41, 2596 – 2599.

3. C.W. Tornøe, C. Christensen, M. Meldal, J. Org. Chem.2002, 67, 3057 – 3064.

4. V. D. Bock, H. Hiemstra, J. H. van Maarseveen, Eur. J. Org. Chem. 2006, 51 – 68.

5. P. Wu, V. V. Fokin, Aldrichim. Acta 2007, 40, 7 – 17.

6. W. H. Binder, R. Sachsenhofer, Macromol. Rapid Commun. 2007, 28, 15 – 54.

7. J.-F. Lutz, Angew. Chem. Int. Ed. 2007, 46, 1018 – 1025.

8. H. C. Kolb, K. B. Sharpless, Drug Discov. Today 2003, 8, 1128 – 1137.

9. R. Breinbauer, M. Köhn, Chembiochem 2003, 4, 1147 –1149.

10. QSAR Comb. Sci. 26, 2007, No. 11-12, 1135 – 1144.



© 1991 - 2014 ENAMINE