Piperidine is preferred to morpholine for Fmoc cleavage in solid phase glycopeptide synthesis as exemplified by preparation of glycopeptides related to HIV gp120 and mucins

Protected derivatives of the Tn antigens [Fmoc-Ser/Thr(Ac(3)GalNAc alpha)-OH, compounds 5 and 8] have been prepared by glycosylationlation of Fmoc-Ser/Thr-OAllyl with 3,4,6-tri-O-acetyl-2-azido-2-deoxy-D-galactopyranosyl chloride (2), followed by conversion of the azido group to an acetamide and deallylation. The derivatives 5 and 8 were used for solid phase synthesis of glycopeptides related to HIV gp120 and mucins. In these syntheses piperidine was found to give efficient Fmoc removal whereas deprotection with morpholine was slow and incomplete for some steps. In contrast to previous concerns beta-elimination and epimerization of glycopeptide stereocenters was not encountered when piperidine was used for Fmoc deprotection. However, it was found that for glycopeptides which contained cysteine residues, de-O-acetylation with methanolic ammonia had to be performed before side-chain deprotection and cleavage from the solid phase. Copyright (C) 1996 Elsevier Science Ltd