Glycoconjugates cycloaddition

Click chemistry has been particularly active in various fields this year. For example, ample applications of click chemistry have been seen in carbohydrate chemistry. Various /weiido-oligosacchardies and amino acid glycoconjugates were synthesized via an intermolecular 1,3-dipolar cycloaddition reaction using easily accessible carbohydrate and amino acid derived azides and alkynes as building blocks <06JOC364>. The iterative copper(I)-catalyzed... 

A. Dondoni and A. Marra, Addressing the scope of the azide-nitrile cycloaddition in glycoconjugate chemistry. The assembly of C-glycoclusters on a calix[4] arene scaffold through tetrazole spacers, Tetrahedron, 63 (2007) 6339-6345. 

A. Yashiro, Y. Nishida, M. Ohno, S. Eguchi, and K. Kobayashi, Fullerene glycoconjugates A general synthetic approach via cycloaddition of per-O-acetyl glycosyl azides to [60]fullerene, Tetrahedron Lett., 39 (1998) 9031-9034. 

A. Dondoni and A. Marra, Synthesis of [60]fulleropyrrolidine glycoconjugates using 1, 3-dipolar cycloaddition with C-glycosyl azomethine ylides, Tetrahedron Lett., 43 (2002) 1649-1652. 

H. Isobe, K. Cho, N. Solin, D. B. Werz, P. H. Seeberger, and E. Nakamura, Synthesis of fullerene glycoconjugates via a copper-catalyzed Huisgen cycloaddition reaction, Org. Lett., 9 (2007) 4611-4614. 

The formation of CC bonds to prepare glycoconjugates has also gained some attention. For example, Diels-Alder cycloaddition has allowed the preparation of synthetic glycoproteins [144] and the construction of a synthetic vaccine candidate against Neisseria meningitidis A [145], These methods relied on a pretagging step to create suitable protein reactants. 

Glycosyl triazoles have been prepared from glycosyl azides by different authors [146,147] using Cu(I)-catalysed Huisgen cycloaddition. The same reaction has been employed for the preparation of polyvalent glycoconjugate clusters (Scheme 35). For example, treatment of 0-protected glucopyranosyl... 

In 2002, Cavaleiro et al. [38] developed the stereoselective synthesis of glycoconjugated isoxazoUdine-fused chlorines (potential photosensitizers in photodynamic cancer therapy) by 1,3-dipolar cycloadditions of meso-tetrakis(pentafluorophenyl)porphyrin (83) with glycosyl nitrones 41-43 and 84. In all cases of sugar moieties, the configuration of the major products 85 indicated an endo addition, as shown in Fig. 18. 

Recently, Wittmann and co-workers reported the one-pot procedure for di-azo transfer and azide-alkyne cycloaddition reaction. As shown in Scheme 21 the divalent glycoconjugate 104 was obtained in excellent yield from amine 103 without the need for isolation of the azide intermediate. Similarly, Moses et al. reported on the efficient conversion of aromatic amines into 12 3-triazoles [75]. 

Ning X, Guo J, Wolfert MA, Boons GJ (2008) Visualizing metabolically labeled glycoconjugates of living cells by copper-free and fast Huisgen cycloadditions. Angew Chem Int Ed 47 2253-2255... 

Copper-catalyzed azide-alkyne cycloadditions have become increasingly popular due to their almost quantitative formation of 1,4-substituted triazoles, regioselectively, and the remarkable functional group tolerance, which is important when dealing with peptides or peptidomimetics. The majority of publications on dipolar cycloaddition reactions in peptide chemistry has focused on the CuAAC and reported peptide bond isosteres, side-chain functionalization, glycoconjugation, macrocyclization and isotopic labeling of peptides. We will most likely see an inaeasing number of applications where peptides are modified by dipolar cycloadditions in the future. 

Although the azide-alkyne [3+2] cycloaddition (cf. Chapter 9) is known in carbohydrate chemistry for more than 50 years, its application for the preparation of glycoconjugates became particularly attractive with the development of the copper(I)-catalyzed variant by Meldal and Sharpless. The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) enables the regioselective formation of 1,4-disubstituted 1,2,3-triazoles under very mild conditions even in a biological context. However, the cellular toxicity of the copper catalyst precludes applications wherein cells must remain viable. Therefore, as an alternative... 

Fig. 13 Scheme for the stepwise cycloaddition reaction. Shoda s activation protocol followed by a CuAAC reaction with a tetrazine-alkyne bi-functional linker, which allowed the following copper free strain promoted final glycoconjugation. ... 

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