C-linked disaccharide analogue of the Thomsen-Friedenreich (T)-epitope α-O-conjugated to L-serine

Abstract

Condensation of a silylated β-D-galactopyranosylaldehyde (3) with isolevoglucosenone (4) in the presence of Et2AlI provided bicyclic enone 5. Subsequent addition of BnNHOMe gave adduct 6, which was converted into 4-O-acetyl-1,6-anhydro-3-C-[(1R)-1,3,4,5,7-penta-O-acetyl-2,6-anhydro-D-glycero- L-manno-heptitol-1-C-yl]-2-azido-2,3-dideoxy-β-D-galacto-hexopyranose after liberation of the 2-amino group, its transformation into a 2-azido moiety, desilylation, and peracetylation. Ring-opening of the 1,6-anhydro galactopyranosyl unit and O-glycosidation with Fmoc-Ser-O-tBu afforded a 5:1 mixture of α- and β-galactosides. Treatment with CH3COSH gave pure N-[(9H-fluoren-9-ylmethoxy)carbonyl]-{4,6-di-O-acetyl-3-C-[(1R)-2,6- anhydro \cf0 cf2 1,3,4,5,7-penta-O-acetyl-D-glycero-L-manno-heptitol-1-C-yl]-2- [(N-acetyl)-amino]-2,3-dideoxy-α-D-galactopyranosyl}-L-serine tert-butyl ester (2), a protected form of a C-disaccharide analogue of the Thomsen-Friedenreich (or T) epitope (β-D-Galp-(1→3)-α-D-Gal- NAcp) α-O-conjugated to L-serine. © 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.