ON-RESIN SOLID-PHASE SYNTHESIS OF ASPARAGINE N-LINKED GLYCOPEPTIDES -USE OF N-(2-ACETOXY-4-METHOXYBENZYL) (ACHMB) ASPARTYL AMIDE-BOND PROTECTION TO PREVENT UNWANTED ASPARTIMIDE FORMATION

The N-(2-acetoxy-4-methoxybenzyl) (AcHmb) backbone amide-protecting gr oup has been applied in an on-resin solid-phase synthesis of asparagin e N-linked glycopeptides. Backbone protection of the -Asp(OAllyl)-Ala- aspartyl amide bond suppressed the formation of aspartimide during bo th the initial chain assembly and the subsequent activation and glycos ylation of the aspartyl beta-carboxy group. A 1.1-1.25 mole excess of glycosylamine coupled quantitatively, with minimal side reaction, to t he activated aspartyl beta-carboxy group of the fully assembled backbo ne-protected peptide-resin. A parallel synthesis without backbone amid e protection produced substantial aspartimide peptide, particularly du ring the initial chain assembly.