3 Synthetic routes of 1,2,3-triazole ring systemTriazolering system could be prepared by different synthetic methodologies 1- 1,3-Dipolar cycloaddition reactions of azides2- The Copper-CatalyzedAzide-Alkyne Cycloaddition (CuAAC)3- The Ruthenium-CatalyzedAzide-Alkyne Cycloaddition (RuAAC) 1.4 Click Chemistry The click chemistry approach invented by Sharpless 29usingcopper (I)-catalyzed azidealkyne cycloaddition (CuAAC) has resulted in theproduction of large number of 1, 4-disubstituted 1, 2, 3-triazoles in very highyields 30. The copper(I)-catalyzed azidealkyne cycloaddition(CuAAC) approach has been widely used in the different spheres of the sciencesuch as bioconjugation 31,oligonucleotide synthesis 32, construction of bolaamphiphilicstructures 33, DNA labelling 34 anddrug discovery 35. In the present scenario of a continuousrequirement for better drugs in shorter times, it is a challenging task toprepare new molecules that combine high activity and selectivity, drug-likenessand good pharmacokinetic properties.
Figure 5 Figure 5 Synthetic routes of 1,2,3- triazole Themost prominent example of click chemistry is the Cu(I)-catalyzed Azide-AlkyneClick Chemistry (CuAAC) reaction36. An Azide-functionalized molecule A reactswith a terminal Alkyne-functionalized molecule B thereby forming a stable conjugate A-B via a Triazole moiety(Fig. 6) Since terminal Alkynes are fairly unreactive towards Azides, theefficiency of a CuAAC reaction strongly depends on the presence of a metalcatalyst such as copper (Cu) in the +1 oxidation state (Cu(I)).
Differentcopper sources and reduction reagents are available however, the Cu(II) saltCuSO4 as copper source in combination with ascorbate as a reduction reagent hasbeen recommended for most biomolecule labeling applications Figure 6 Principle ofCu(I)-catalyzed Azide-Alkyne Click Chemistry(CuAAC).