Susceptibility of glycans to β‐elimination in Fmoc‐based O‐glycopeptide synthesis

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Abstract
In order to investigate the possible extent of beta-elimination occuring in Fmoc-based continuous-flow solid-phase glycopeptide synthesis, the influence of the pK(b) of the base used for N-alpha-deprotection has been studied. A glycosylated pentapeptide was synthesized using 50% morpholine, 10% piperidine or 2% DBU, respectively, in DMF for deprotection. The dehydropentapeptide N-alpha-Ac-Thr-Thr-Delta Aba-Val-Thr-NH2, which would be formed in the case of beta-elimination, was prepared independently and used as a control in HPLC analysis; however, this product 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 similarly 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 glycopeptides were isolated and characterized by H-1-NMR spectroscopy. (C) Munksgaard 1994.