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 which is highly specific, can be carried out in water, and fully bioorthogonal. As a result, it has rapidly established a prominent role in materials science, medicinal, and bioconjugation chemistry.
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.
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.