Scheme 3.

Optimization of the coupling reaction on to a solid support with a model peptidyl-resin. The model tripeptide, Ac-Arg-Pra-Arg-aminohexanoyl-resin, assembled on a Rink-amide resin, was used to optimize the conditions for coupling the azido galactose 2. The various parameters (copper salt, base, solvent, and coupling time) were analyzed; see Table 1 in Supplementary materials. The evolution of the coupling reaction (ratio of starting peptide vs peptide 8) was monitored after the cleavage from the resin and HPLC analysis. Triazole formation was complete within 5 h with 2 eq. of sugar 2. Four eq. of Cu(OAc)₂ or 2 eq. of CuI were both efficient in the presence of 2 eq. of ascorbic acid and 5 eq. of diisopropylethylamine, in DMF containing 30% of pyridine, lutidine, or piperidine