General Methods for α- or β-O-Ser/Thr Glycosides and Glycopeptides. Solid-Phase Synthesis of O-Glycosyl Cyclic Enkephalin Analogues

Robin Polt, Lajos Szabó, Jennifer Treiberg, Yushun Li, Victor J. Hruby

Research output: Contribution to journalArticle

111 Scopus citations

Abstract

O-Linked glycopeptides have been efficiently synthesized using the highly nucleophilic α-imino esters (O'Donnell's Schiff bases) derived from l-serine (3a–c), l-threonine (4a,b), and a dipeptide ester (5). General methodology has been developed which can provide β-glycosides of β-hydroxy-α-amino acid derivatives 6-16 in excellent yield (63–94%) and excellent selectivity (>20:1) using Hanessian's modification or Helferich's modification of the Koenigs-Knorr reaction. Likewise, selective α-glycosylation has been achieved using the in situ anomerization methodology of Lemieux (28,30). The increased nucleophilicity of the serine/threonine hydroxyl has been shown to be due to intramolecular hydrogen bonding to the N=CPh2 moiety. Deprotection of the intermediate Schiff bases has been demonstrated, and the glycosides have been incorporated into fully deprotected O-linked glycopeptides in high yield using either solution-phase peptide methods or solid-phase Fmoc-based technology. The potent glycosylenkephalin analogue 38 has been prepared using the solid-phase methodology.

Original languageEnglish (US)
Pages (from-to)10249-10258
Number of pages10
JournalJournal of the American Chemical Society
Volume114
Issue number26
DOIs
StatePublished - Dec 1 1992

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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