Preparation of Tn and sialyl Tn building blocks used in Fmoc solid-phase synthesis of glycopeptide fragments from HIV gp120

The synthesis of novel building blocks corresponding to the Tn [alpha-D-GalNAc-(1-->O)-Thr] and sialyl Tn [alpha-D-Neu5Ac-(2-->6)-alpha-D-GalNAc-(1-->O)-Thr] epitopes is described. The Tn building block was prepared from 4-methylphenyl 2-azida-2-deoxy-1-thio-beta-D-galactopyranoside in four steps (42% yield) and carries tert-butyldimethylsilyl protective groups for the GalNAc moiety. Further conversion into a sialyl Tn building block, having acetyl protective groups for the sialic acid unit, was achieved in an additional four steps (37% yield). Both building blocks were used, in low excess (<20%), for Fmoc solid-phase synthesis of glycopeptide fragments from HIV gp120. The silyl protective groups of the Tn epitope were completely removed simultaneously with acid catalyzed cleavage of the glycopeptides from the solid phase. Hydrolysis of the sialic acid residue was not encountered during acid catalyzed cleavage of the sialyl Tn glycopeptide from the solid phase or during purification, even though glycosides of sialic acid are labile under acidic conditions. Copyright (C) 1996 Elsevier Science Ltd