Protected-mode synthesis of N-linked glycopeptides: single-step preparation of building blocks as peracetyl glycosylated NαFmoc asparagine OPfp esters

Abstract

The preparation of N^α-(fluoren-9-ylmethoxycarbonyl)asparagine pentafluorophenyl esters (N^α-Fmoc-Asn-OPfp) glycosylated with per-O-acetylated β-D-glucose, N-acetyl-β-D-glucosamine, β-D-mannose, 4-O-β-D-glucopyranosyl-β-D-glucose (cellobiose), 4-O-β-D-galactopyranosyl-β-D-glucose (lactose) and 4-O-α-D-glucopyranosyl-β-D-glucose (maltose) is described. The per-O-acetylated glycosylamines were treated selectively with the key compound N^α-Fmoc-Asp(Cl)-OPfp 2, to give, in a single step, the glycosylated building blocks. The acid chloride 2 was prepared in a quantitative one-pot reaction from commercially available N^α-Fmoc-Asp(OBu^t)-OPfp 1. The acid stability of the N-glycosidic linkage was investigated. The building block 7, containing a maltose moiety, was used in the synthesis of a glycosylated D-Ala¹ Peptide-T amide analogue 14. CD spectra were recorded in 85% TFE. All compounds were fully characterized by ¹H and ¹³C NMR spectroscopy.