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, OR BETA-D-GLC

Five trisaccharide derivatives designed for detailed exploration of th e 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 acc eptor octyl benzyl-2-O-(3,6-di-O-benzyl-2-deoxy-2-phthalimido- beta-D- glucopyranosyl)-alpha-D-mannopyranoside was synthesized by condensatio n of 4-O-acetyl-3, 6-di-O-benzyl-2-deoxy-2-phthalimido-alpha,beta-D- g lucopyranosyl 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-a lpha-D-glucopyranosyl trichloroacetimidate were used as the glycosyl d onors in the syntheses of 1 and 5. The modified galactosyl derivatives required subtle anomeric activation. Suitable donors for 2 turned out to be ,6-tri-O-acetyl-4-deoxy-alpha-D-xylo-hexopyranosyl trichlorortc etimidate and ethyl 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-alp ha,beta-D- galactopyranoside; and for 4, O-acetyl-4-deoxy-4-fluoro-alp ha-D-galactopyranosyl trichloroacetimidate. It was concluded that thio glycosides were most appropriate for stereoselective coupling of activ ated synthons (carrying deoxy or O-methyl groups), whereas trichloroac etimidates gave high yields with deactivated (fluorine-containing) syn thons. (C) 1996 Elsevier Science Ltd.