Synthesis of Hex p-(1 → 4)-β- d-Glc pNAc-(1 → 2)-α- d-Man p-(1 → O)(CH 2) 7CH 3 probes for exploration of the substrate specificity of glycosyltransferases: Part I, Hex = β- d-Gal, 4-deoxy-β- d-Gal, 4- O-methyl-β- d-Gal, 4-deoxy-4-fluoro-β- d-Gal, or β- d-Glc

Abstract

Five trisaccharide derivatives designed for detailed exploration of the acceptor specificity of glycosyltransferases involved in termination of N-acetyllactosamine-type structures have been synthesized: β- d-Gal p-(1 → 4)-β- d-Glc pNAc-(1 → 2)-α- d-Man p-(1 → O)(CH 2) 7CH 3 ( 1), 4-deoxy-β- d-Gal p-(1 → 4)-β- d-Glc pNAc-(1 → 2)-α- d-Man p-(1 → O)(CH 2) 7CH 3 ( 2), 4- O-methyl-β- d-Gal p-(1 → 4)-β- d-Glc pNAc-(1 → 2)-α- d-Man p-(1 → O)(CH 2) 7CH 3 ( 3), 4-deoxy-4-fluoro-β- d-Gal p-(1 → 4)-β- d-Glc pNAc-(1 → 2)-α- d-Man p-(1 → O)(CH 2) 7CH 3 ( 4), and β- d-Glc p(1 → 4)-β- d-Glc pNAc-(1 → 2)-α- d-Mann p-(1 → O)(CH 2) 7CH 3 ( 5). A general disaccharide acceptor octyl was synthesized by condensation of 4- O-acetyl-3,6-di- O-benzyl-2-deoxy-2-phthalimido-α,β- dglucopyranosyl trichloroacetimidate with octyl 3,4,6-tri- O-benzyl-α- d-mannopyranoside, followed by deacetylation. 2,3,4,6-Tetra- O-acetyl-α- d-galactopyranosyl trichloroacetimidate and 2,3,4,6-tetra- O-acetyl-α- d-glucopyranosyl trichloroacetimidate were used as the glycosyl donors in the syntheses of 1 and 5. The modified galactosyl derivatives required subtle anomeric activation. Suitable donors for 2 turned out to be 2,3,6-tri- O-acetyl-4-deoxy-α- d- xylo-hexopyranosyl trichloroacetimidate and ethyl 2,3,6-tri- O-acetyl-4-deoxy-1-thio-α,β- d- xylo-hexopyranoside; for 3, ethyl 2,3,6-tri- O-acetyl-4- O-methyl-1-thio-α,β- d-galactopyranoside; and for 4, 2,3,6-tri- O-acetyl-4-deoxy-4-fluoro-α- d-galactopyranosyl trichloroacetimidate. It was concluded that thioglycosides were most appropriate for stereoselective coupling of activated synthons (carrying deoxy or O-methyl groups), whereas trichloroacetimidates gave high yields with deactivated (fluorine-containing) synthons.