Solid-phase synthesis of core 3 and core 6 O-glycan-linked glycopeptides by benzyl-protection method

Abstract Core 3 and core 6 O -glycoamino acids were prepared in a protected form suited for Fmoc solid-phase peptide synthesis (SPPS). An N -trichloroacetyllactosamine derivative ( 2 ) was used as a highly β-selective glycosyl donor in 3-O-glycosylation of acceptors 3 / 4 and in 6-O-glycosylation of acceptors 5 / 6 . Zn reduction of trisaccharides 7 / 8 and 13 / 14 was followed by acetylation to readily transform trichloroacetamido and azido groups to acetamido groups. Selective deprotection by Pd(0)-catalysis afforded core 3 O -glycan building blocks 11 / 12 and core 6 O -glycan building blocks 17 / 18 . Usefulness of these building blocks for SPPS was demonstrated by the syntheses of the core 3-linked MUC2 tandem repeat glycopeptide and the core 6-linked glycopeptide segment of MUC6. The synthetic glycopeptides detached from the resin were debenzylated under the ‘low-acidity TfOH’ conditions.