SUSCEPTIBILITY OF GLYCANS TO BETA-ELIMINATION IN FMOC-BASED O-GLYCOPEPTIDE SYNTHESIS

In order to investigate the possible extent of beta-elimination occuri ng in Fmoc-based continuous-flow solid-phase glycopeptide synthesis, t he influence of the pK(b) of the base used for N-alpha-deprotection ha s been studied. A glycosylated pentapeptide was synthesized using 50% morpholine, 10% piperidine or 2% DBU, respectively, in DMF for deprote ction. The dehydropentapeptide N-alpha-Ac-Thr-Thr-Delta Aba-Val-Thr-NH 2, which would be formed in the case of beta-elimination, was prepared independently and used as a control in HPLC analysis; however, this p roduct was not formed under any of the deprotection conditions applied . Furthermore, a 23 amino acid long glycopeptide from human intestinal mucin was prepared using 2% DBU as a base for Fmoc cleavage, and simi larly no beta-elimination was observed. The glycopeptide products were subjected to a prolonged treatment with sodium hydroxide in methanol/ water without significant formation of byproducts, and the pure glycop eptides were isolated and characterized by H-1-NMR spectroscopy. (C) M unksgaard 1994.