1.2.3- Triazoles click chemistry applications

It was clear from this early work that mass spectrometric analysis would be the most appropriate technique to detect hit compounds for in situ Click chemistry applications. Although the DIOS-MS method was able to directly detect the low quantity of triazole product conversion in the presence of large amounts of protein and parent fragments, the sensitivity for this measurement was very low, with a poor signal-to-noise ratio. It was therefore both logical and desirable to optimize the sensitivity and selectivity of the MS... 

Click chemistry also found applications in peptides and peptidomimetics. Alkyne-azide cycloaddition between two peptide strands provided an efficient convergent synthesis of triazole ring-based P-tum mimics <07CC3069>. The synthesis of a-substituted prolines has been accomplished by microwave-assisted Huisgen 1,3-dipolar cycloaddition between azides and orthogonally protected a-propynyl proline in the presence of Cu(I) sulfate <07SL2882>. The synthesis of new trifluoromethyl peptidomimetics with a triazole moiety has been reported <07TL8360>. 

Click chemistry has proved to be a versatile strategy and has undergone a spectacular development in the last few years, as a broad spectrum of applications has been found. Thus, for example, this concept has been applied to the preparation of polymers [137-140], dendrimers [141-144], glycoclus-ters [145] and pharmacophores [118]. The 1,2,3-triazole moiety was found to be a mimic of the amide moiety, characterized by an enhanced stability towards hydrolysis and oxidations [118]. 

This new strategy is the application of Sharpless click chemistry [475]. Coil-man, Devaraj, and Chidsey first applied this chemistry to the exposed surface of SAMs (Fig. 12). They demonstrated that this reaction proceeds completely at room temperature in aqueous solvent. The reaction is extremely specific with high yield, indicating that this offers a convenient method to modify well-defined electrode surfaces [97]. This reaction uses the formation of triazoles through the classic... 

Ganesh V, Sudhir VS, Kundu T, Chandrasekaran S (2011) 10 years of click chemistry synthesis and applications of ferrocene-derived triazoles. Chem-Asian J 6(10) 2670-2694. doi 10.1002/asia. 201100408... 

Synthesis of new materials based on click chemistry between a terminal acetylene and an azide unit to form a triazole continues to be of great interest. The Click-cycloaddition requires Cu(I) species. The Cu(I) species can be generated easily by in situ reduction of CUSO4 with ascorbic acid (eq 27). Application of microwave (MW) energy to promote this useful reaction has helped to reduce reaction times and increase reaction rates considerably. 

Owing to the popularity and vast modularity of the copper(l)-catalyzed azide-alkyne cycloaddition (CuAAC) [4,5], so-called click chemistry [24] (Fig. 1), many more 1,2,3-triazole-based anion receptors have been reported during the past 3 years (2008-2011). Reviews [25, 26] have been published to cover this new moiety in anion receptor chemistry. Therefore, this chapter will focus on triazole-based anion receptors that have not been reviewed to date. In addition, applications including sensors, ion-selective electrodes, catalysis, anion transport, and anion regulation, as well as their use in interlocked molecules, will be discussed. 

Today, CuAAC and copper-free click chemistry are serving as complementary approaches to modify biomolecules for both in vitro and in vivo applications. In this chapter, we will highlight the recent applications of these triazole-forming reactions to the imaging and profiling of biomolecules. Comprehensive reviews of click chemistry-based approaches for bioconjugation have been published recently [12, 29]. 

The synthesis of triazoles by 1,3-dipolar cycloaddition between azides and alkynes has been extensively studied recently with numerous synthetic applications in the field of click chemistry. However, the Huisgen cycloaddition between azides 39 and alkenes 40 (Scheme 41.9) although less studied offers interesting opportunities for the stereoselective formation of C N bonds in the context of natural products synthesis. The triazolines 41 thus formed are in fact good precursors of aziridines via ring contraction and expulsion of N2. 

In a recent review article [35], several methods of syntheses of 1,2,3-triazoles using click chemistry and its applications aimed at finding new lead candidates against pathologies such as cancer, AIDS, and Alzheimer s disease have been elegantly described. 

An exhaustive review [47] on click chemistry in Drug Development and Diverse Chemical Biology applications and another review [48] pertaining to the biolog-ical properties of lH-1,2,3- and 2//-1,2,3-triazoles have recently been published. There have also been many review articles that summarize the impact of click chemistry in drug discovery particularly in the early stages [49, 50]. 

I 2 Applications of Click Chemistry in Drug Discovery and Development 2.23.7 Anticancer Activity of 4p-Triazole-Podophyiiotoxin... 

Among the different procedures that can be considered as click chemistry reactions, cycloadditions, and particularly the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (CuAAc) between azides and terminal alkynes to form 1,2,3-triazoles, are the most widely used. This reaction has found applications across many diverse research areas. In the following sections, the potential of this click reaction and its applications are reviewed. 

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