Total Synthesis of Mannosyl Tryptophan and Its Derivatives

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Abstract
Glycosylation is one of the most important post- or co-translational modifications of proteins, which affects the biological activities of the parent proteins by influencing the higher-order structure. Recently, a highly novel variant of glycoproteins that incorporate a C-glycosylated amino acid was identified in various proteins. The total synthesis of one such C-glycosyl amino acid, namely, C 2-α-D-C-mannosylpyranosyl-L-tryptophan and related peptides were successfully achieved. The mannose and tryptophan moieties were connected via ring opening of benzyl-protected 1,2-anhydro-mannose by a lithiated indole derivative. After the functional group conversion and deprotection steps, the glyco-amino acid was synthesized in a concise and stereoselective manner, in high overall yields. The stereoisomer, C 2-α-D-C-glycosylpyranosyl-L-tryptophan was synthesized in a similar way. Furthermore, it was revealed that the intermediate azido acid can serve as a useful building block for peptide elongation. A synthetic route for the peptide bond formation of a glycopeptide, without protection of the hydroxyl groups, using the triazine salt derivative as a coupling reagent is also reported.