SYNTHESIS OF HEX P-(1-]4)-BETA-D-GLC PNAC-(1-]2)-ALPHA-D-MAN P-(1-]O)(CH2)(7)CH3 PROBES FOR EXPLORATION OF THE SUBSTRATE SPECIFICITY OF GLYCOSYLTRANSFERASES .1. HEX=BETA-D-GAL, 4-DEOXY-BETA-D-GAL, 4-O-METHYL-BETA-D-GAL, 4-DEOXY-4-FLUORO-BETA-D-GAL, O

摘要

Five trisaccharide derivatives designed for detailed exploration of the acceptor specificity of glycosyltransferases involved in terminition of N-acetyllactosamine-type structures have been synthesized: beta-D-Galp-(1 --> 4)-beta-D-GlcpNAc-(1 --> 2)-alpha-D-Manp-(1 --> 0)(CH2)(7)CH3 (1), 4-deoxy-beta-D-Galp-(1 --> 4)-beta-D-GlcpNAc-(1 --> 2)-alpha-D-Manp-(1 --> 0)(CH2)(7)CH3 (2), 4-O-methyl-beta-D-Galp-(1 --> 4)-beta-D-GlcpNAc-(1 --> 2)-alpha-D-Manp-(1 --> 0)(CH2)(7)CH3 (3), 4-deoxy-4-fluoro-beta-D-Galp-(1 --> 4)-beta-D-GlcpNAc-(1 --> 2)-alpha-D-Manp-(1 --> 0)(CH2)(7)CH3 (4), and beta-D-Glcp- (1 --> 4)-beta-D-GlcpNAc-(1 --> 2)-alpha-D-Manp-(1 --> 0)(CH2)(7)CH3 (5). A general disaccharide acceptor octyl 3,4,6-tri-O-benzyl-2-O-(3,6-di-O-benzyl-2-deoxy-2-phthalimido- beta-D-glucopyranosyl)-alpha-D-mannopyranoside was synthesized by condensation of 4-O-acetyl-3, 6-di-O-benzyl-2-deoxy-2-phthalimido-alpha,beta-D- glucopyranosyl trichloroacetimidate with octyl 3,4,6-tri-O-benzyl-alpha-D-mannopyranoside, followed by deacetylation. 2,3,4,6-Tetra-O-acetyl-alpha-D-galactopyran trichloroacetimidate and 2,3,4,6-tetra-O-acetyl-alpha-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-alpha-D-xylo-hexopyranosyl trichlorortcetimidate and ethyl 2,3,6-tri-O-acetyl-4-deoxy-1-thio-alpha,beta-D-xylo- hexopyranoside; for 3, ethyl 2,3,6-tri-O-acetyl-4-O-methyl-1-thio-alpha,beta-D- galactopyranoside; and for 4, 2,3,6-tri-O-acetyl-4-deoxy-4-fluoro-alpha-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. (C) 1996 Elsevier Science Ltd. [References: 33]