Total synthesis of mannosyl tryptophan and its derivatives.
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)-alpha-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)-alpha-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.
Manabe
Shino
S
RIKEN (The Institute of Physical and Chemical Research) Wako-shi, Saitama 351-0198, Japan.
Marui
Yoshihiko
Y
Ito
Yukishige
Y
D008358:Mannose / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D014364:Tryptophan / Q000737:chemistry*
D014364:Tryptophan; D008358:Mannose