An efficient access to protected disialylated glycohexaosyl threonine present on the leukosialin of activated T-lymphocytes

The total synthesis of the threonine-linked core 2 class disialylated hexas accharide in a completely protected form was accomplished for the first tim e. The L-threonine conjugate, N-(9-fluorenylmethoxycarbonyl)-O-{(5-acetomid o-4,7,8,9-tetra-O-benzyl-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyra nosylanic acid)-(2 --> 3)-(2,6-di-O-benzyl-beta-D-galactopyranosyl)-(1 --> 4)-2-acetamido-2-deoxy-3,6-di-O-benzyl-beta-D-glucopyranosyl-(1 --> 6)-[(5- acctamido-4,7,8,9-tetra-O-benzyl-3, 5-dideoxy-D-glycero-alpha-D-galacto-2-n onulopyranosylonic acid)-(2 --> 3)-2,6-di-O-benzyl-beta-D-galactopyranosyl- (1 --> 3)]-2-acetamido-2-deoxy-alpha-D-galactopyranosyl-(1d --> 4c:1f --> 4 e)-dilactone}-L-threonine allyl ester was synthesized via stereocontrolled glycosylations employing readily accessible monosaccharidic blocks; t-butyl -diphenylsilyl-2-azido-2-deoxy-3, 6-di-O-benzyl-beta-D-glucopyranose, N-(9- fluorenylmethoxycarbonyl)-O-(2-azir-butylditnethylsilyl-2-deoxy-alpha-D-gal actopyranosyl)-L-threonine allyl ester, 8, 9 and N-(9-fluorenylmethoxycarbo nyl)-O-(2-azido-4,6-O-benzylidene-3-O-chloroacetyl-2-deoxy-alpha-D-galactop yranosy;)-L-threonine allyl ester. For the introduction of the amino acid. the azide group was used to temporarily mask the amino group of GalNAc so a s to obtain an alpha-glycosidic linkage without participation from the C-2 substituent. The threonine was attached to the sugar unit at the monosaccha ride stage to avoid loss of oligosaccharide at a later stage. The Fmoc and allyl ester protected amino acid at the reducing end facilitates efficient glycopeptide synthesis on solid-phase support. (C) 2000 Elsevier Science Lt d. All rights reserved.