General methods for α- Or β-O-Ser/Thr glycosides and glycopeptides. Solid-phase synthesis of O-glycosyl cyclic enkephalin analogues

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

Research output: Contribution to journalArticle

111 Citations (Scopus)

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
StatePublished - 1992

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Glycosides
Solid-Phase Synthesis Techniques
Schiff Bases
Glycopeptides
Enkephalins
Threonine
Serine
Esters
Glycosylation
Hydroxy Acids
Dipeptides
Hydrogen Bonding
Hydroxyl Radical
Peptides
Amino acids
Hydrogen bonds
Technology
Derivatives
Amino Acids

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

General methods for α- Or β-O-Ser/Thr glycosides and glycopeptides. Solid-phase synthesis of O-glycosyl cyclic enkephalin analogues. / Polt, Robin L; Szabó, Lajos; Treiberg, Jennifer; Li, Yushun; Hruby, Victor J.

In: Journal of the American Chemical Society, Vol. 114, No. 26, 1992, p. 10249-10258.

Research output: Contribution to journalArticle

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AU - Szabó, Lajos

AU - Treiberg, Jennifer

AU - Li, Yushun

AU - Hruby, Victor J

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