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number of conditions were screened at room temperature in which both solvent and catalystwere varied (Figure 3). CuI/DIPEA system in DMF did not turn out to be suitable for thereaction (entry 1). CuSO 4 -5H 2 O proved to be adequate catalyst yielding 1,3-triazole with99% conversion in 4 h using tBuOH/H 2 O (1:1) as solvent (entry 3) instead of CH 3 CN/H 2 O(1:1).Decreasing catalyst loading to 5 mol % afforded the cycloadduct in 93% conversionbut reaction time needed to be extended to 20 h (entry 4). tBuOH as cosolvent proved to bemandatory for the reaction to occur (entry 6). Optimized reaction conditions correspondedto 10 mol % CuSO 4 -5H 2 O with 100 mol % sodium ascorbate (NaAsc) in tBuOH/H 2 O (1:1).Encouraged by these results, a series of alkyne carbohydrates were examined along withvarious C-terminal azide linker peptides (Figure 4). Cu(I)-catalyzed cycloaddition ofshikimic 7 (entry 1) or quinic [7] (entry 4) N-propargyl amide derivatives with peptides 1and 3 afforded expected C-terminal glycopeptides respectively with 79 and 72% yields.Peptides 2 and 4 can also react efficiently with O-alkyne carbohydrates, such as α-glucose(entry 2) or β-NAc glucosamine (entry 3) compounds, to yield the triazole cycloadductswith excellent conversions.Ac-I-L-K-E-P-V-Y-X-NH N 3+10 mol % CuSO 4 -5H 2 OR 100 mol % NaAscAc-I-L-K-E-P-V-Y-X-NH NtBuOH/H 2 O 1:125°CN NEntryAzide peptide a(X)Alkyne Time Conversion b (Yield) cHO NR1 G4 h 100 % (79 %)HOOHOHOH2 AHOHOOOHO4 h > 93 %OH3 VHOHOONHO4 h > 96 % (78 %)OHOOHN4 S4 h > 99 % (72 %)HOOHOHa Reactions performed on 5 mM scale with a ratio Azide to Alkyne of 1:2. b Conversion determined byHPLC integration on azide consumption. c Isolated yield.Fig. 4. C-Terminal glycopeptides synthesis.In summary, an efficient and reliable two steps synthesis of amine-azide salts has beendescribed. Cu(II) oxidative aminolysis has been applied to the synthesis of C-terminal azidelinker peptides. Finally Cu(I)-catalysed cycloaddition can be carried out on unprotectedC-terminal azide linker peptides with various carbohydrate derivatives and analogues withhigh yields leading to C-terminal glycopeptide conjugates.AcknowledgmentsWe thank financial support from CNRS, Région Nord-Pas-de-Calais, Institut Pasteur de Lille andEndotis Pharma Inc. We acknowledge CSB platform (http://csb.ibl.fr) for technical support.References1. Tornøe, C.W., Christensen, C., Meldal, M. J. Org. Chem. 67, 3057-3064 (2002).2. Rostovtsev, V.V., et al. Angew. Chem. Int. Ed. 41, 2596-2599 (2002).3. Lin, H., Walsh, C.T. J. Am. Chem. Soc. 126, 13998-14003 (2004).4. Wan, Q., Chen, J., Chen, G., Danishefsky, S.J. J. Org. Chem. 71, 8244-8246 (2006).5. a) Carboni, B., Benalil, A., Vaultier, M. J. Org. Chem. 58, 3736-3741 (1993); b) Tamanini, S.,Rigby, E.J., Motevalli, M., Todd, M.H., Watkinson, M. Chem. Eur. J. 15, 3720-3728 (2009).6. Brunsveld, L., et al. Chem. Eur. J. 11, 2756-2772 (2005).7. a) Grandjean, C., Gras-Masse, H., Melnyk, O. Chem. Eur. J. 7, 230-239 (2001); b) Angyalosi, G., etal. Bioorg. Med. Chem. Lett. 12, 2723-2727 (2002).217