Convenient high yield and stereoselective synthesis of O-glycopeptides using N-α-Fmoc-Tyr/Ser[β-D-Glc(OAc)4]OPfp generated in solution

Abstract

Fmoc-AA-OPfp (AA=Tyr or Ser) (1 equiv) was reacted with β-D-Glc(OAc)5 (6 equiv) in the presence of BF 3.Et2O (6 equiv) in CH2Cl2 at room temperature for 2 h, and the glycosylation reaction mixture was used directly to couple to the amino group of the peptide resin without isolation and purification of the Fmoc-AA[β-D-Glc(OAc)4]-OPfp. Moreover, the -OAc protecting groups of glucose was removed just prior to releasing the peptide from the resin using 6 mM NaOMe in 85% DMF-MeOH. The crude product obtained by TFA cleavage contained >90% of the target O-glycopeptide, and the 500 MHz 1H NMR analysis revealed that the glycosylation reaction was nearly stereoselective (>97% β-anomer). This method is rapid and stereoselective, and can now be exploited for the routine synthesis of O-glycopeptides. © 2003 Elsevier Ltd. All rights reserved.