Huisgen Cycloaddition Click Chemistry

The Huisgen cycloaddition reaction of azides with alkynes to produce triazoles was used to produce HA hydrogels and to encapsulate yeast cells during crosslinking. In this method, azide and alkyne functional groups were installed on HA using EDC chemistry. The hydrogel 

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Ramachary, D.B. Barbas, C.R III (2004) Towards Organo-Click Chemistry Development of Organocatalytic Multicomponent Reactions Through Combinations of Aldol, Wittig, Knoevenagel, Michael, Diels-Alder and Huisgen Cycloaddition Reactions. Chemistry A European Journal, 10, 5323-5331. 

There are four different chemical reactions that have been used to crosslink polymers with peptide sequences (Fig. 6.8) (i) amide bond formation (ii) Michael-type addition (iii) Huisgen cycloaddition (click reaction) and (iv) radical polymerisation. The amide bond formation follows typical solid phase peptide synthesis (SPPS) protocols and does not require functionalisation of the termini of the peptide sequence. Fluorenyhnethoxycarbonyl (Fmoc) protection of the N-terminus allows attachment of the peptide sequence to an amine-bearing polymer. After removal of the Fmoc group, the amine-terminated peptide-polymer conjugate can be reacted with a second polymer bearing carboxylic acid functionalities using the same coupling chemistry (Maier et al, 2011). For Michael-type additions the peptide... 

Huisgen 1,3-dipolar cycloaddition (click chemistry) to form the 1,2,3-triazole ring (Scheme 50(a)). ... 

Kappe and co-workers proposed an application of a microwave-assisted Huisgen 1,3-dipolar cycloaddition of terminal acetylenes and azides 70, imder Cu(I) catalysis, as an example of click chemistry to obtain a collection of... 

A specific peptide sequence for nuclear targeting (NLS) has been conjugated to gold NRs via click chemistry. In particular, a thiol with an azide end group has been reacted via Huisgen 1,3-dipolar cycloaddition to an alkyne-terminated NLS peptide and then anchored to CTAB-protected gold NRs.250... 

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>. 

A recent very flexible approach for the preparation of TSOS has been published by Liebscher [34], It relies on a two step procedure with one so-called click chemistry step, which is a regioselective copper catalyzed [3 + 2] Huisgen cycloaddition between an azide and a terminal alkyne, followed by quatemarisation of resulting triazoles. Both reagents can be functionalized prior to cyclisation and furthermore such triazolium synthesis can tolerate a large variety of substituents owing to its chemoselectivity (Fig. 14). 

In this context, click chemistry has been explored as a method for rapid synthesis of compound libraries. In click chemistry, compounds are rapidly synthesized through heteroatom links by a set of powerful, highly reliable, and selective reactions, such as Huisgen s 1,3-dipolar cycloaddition reactions. Click chemistry uses chemical building blocks with built-in high-energy content to drive a spontaneous and irreversible linkage reaction with appropriate complementary sites in other blocks. 

Another chemoselective ligation reaction is the [2 + 3] cycloaddition between an azide and an alkyne. This reaction has been discovered by Huisgen and was lately named click-reaction by Sharpless and Meldal [180, 181]. Whereas the Huisgen 1,3-dipolar cycloaddition leads to two isomeric triazole products at high temperature, click chemistry is performed under the catalysis of Cu(I), thus changing the reaction mechanism from a concerted to a step-wise route and resulting in the formation of the 1,4-substituted triazole as the only product, usually isolated in high yields [174, 182-186],... 

The scope and utility of these chemical reporters is expanding. The application of the Huisgen [3 + 2] cycloaddition or click chemistry reaction provides a complementary approach to the Staudinger ligation for... 

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