Chemical Synthesis of Difucosylated Glycopeptide by the Combination of Substituted Benzyl and Levulinoyl Protecting Groups

Fmoc-Asn bearing a levulinoyl-protected difucosyl tetrasaccharide was prepared using substituted benzyl group for other hydroxy groups. This unit was employed in the solid-phase peptide synthesis (SPPS) of a scorpion toxin segment. The fucosyl linkage survived TFA treatment after SPPS owing to acid stabilization by the levulinoyl group. The resulting glycopeptide was ligated with other segments in a one-pot manner, followed by hydrazine-mediated removal of the levulinoyl groups and disulfide bond formation, successfully affording the desired toxin.