Synthesis of β-D-Galp-(1→4)-β-D-GlcpNAc-(1→2)-α -D-Manp-(1→O)(CH2)7CH3 mimics to explore the substrate specificity of sialyltransferases and trans-sialidases

Abstract

Eleven trisaccharide octyl glycosides related to the N-glycan sequence β-D-Galp-(1→4)-β-D-GlcpNAc-(1→2)-α-D-Manp-(1→O) (CH2)7CH3 (1) designed for detailed exploration of the acceptor specificity of α-2,3- and α -2,6-sialyltransferases as well as trans-sialidases, have been synthesised: β-D-Galp-(1→4)-β-D-GlcpNPr-(1→2)-α-D-Manp-(1→O) (CH2)7CH3 (2), β-D-Fucp-(1→4)-β -D-GlcpNR-(1→2)-α-D-Manp-(1→O)-(CH2) 7CH3 (3, R = Ac; 4, R = Pr), 6-amino-6-deoxy-β -D-Galp-(1→4)-β-D-GlcpNR-(1→2)-α-D-Manp-(1→O)(CH 2)7CH3 (5, R = Ac; 6, R = Pr), 2-deoxy-β-D-Galp-(1→4)-β-D-GlcpNR-(1→2)-α -D-Manp-(1→O)(CH2)7CH3 (7, R = Ac; 8, R = Pr), β-D-GalpNR1-(1→4)-β-D-GlcpNR-(1→2)-α -D-Manp-(1→O)-(CH2)7CH3 (9, R = R 1 = Ac; 10, R = R1 = Pr; 11, R = Ac, R1 = Pr; 12, R = Pr, R1 = Ac). All trisaccharides were obtained by condensation of suitably modified glycosyl donors based on imidates or thioglycosides with the single disaccharide acceptor octyl (3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-D-glucopyranosyl)-(1→2)-3,4, 6-tri-O-benzyl-α-D-manno-pyranoside, followed by deprotection. For the trisaccharides containing an N-acylated glucosamine as well as an N-acylated galactosamine unit, use was made of a combination of N-phthaloyl and N-dimethylmaleoyl protection. © Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.