Automated, solid-phase synthesis of C-neoglycopeptides: Coupling of glycosyl derivatives to resin-bound peptides

A fully automated solid-phase synthesis of C-neoglycopeptides has been deve loped using a convergent strategy. In this approach, C-glycoside derivative s (3 and 4) were coupled to resin-bound peptides using a peptide synthesize r. An advantage of the convergent approach is the ability to introduce mult iple glycoside units late in the synthesis. The approach presented is highl y versatile and efficient and could be used for building C-neoglycopeptide libraries. In our study, neoglycopeptides 5 and 6 were obtained from the co upling of C-glycoside derivatives (3 and 4) to a free amino group of the si de chain of short peptides (2, n = 1 and 3). A similar approach was develop ed for the synthesis of bivalent neoglycopeptides 8 and 9 in an automated m anner. The successful syntheses of C-neoglycopeptides 5, 6, 8, and 9 are th e first examples of coupling of C-glycosyl carboxyl derivatives to the amin o groups of the side chains of resin-bound peptides.