Synthesis of 2-acetamido-6-O-(5-acetamido-3,5-dideoxy-β-D-glycero-D-galacto-2-nonulo-pyranosylonic acid)-2-deoxy-D-glucose [2-acetamido-6-O-(N-acetyl-β-D-neuraminyl)-2-deoxy-D-glucose]

Abstract

Silver triflate-promoted condensation of methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2-chloro-2,3,5-trideoxy-β-D-glycero-D-galacto -2-nonulopyranosonate (9) with benzyl-2-acetamido-2-deoxy-3,4-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-α-D-glucopyranoside, followed by removal of the 1,1,3,3-tetraisopropyldisiloxane-1,3-diyl group and subsequent acetylation, afforded a 4:1 mixture of benzyl 2-acetamido-3,4-di-O-acetyl-2-deoxy-6-O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-β-D-glycero-D-galacto-2-nonulopyranosylonate)-α-D-glucopyranoside (13) and the (2¨6)-α-linked isomer. After selective crystallisation, 13 was obtained in 46% yield based on the precursor of 9, methyl 5-acetamido-2,4,7,8,9-penta-O-acetyl-3,5-dideoxy-D-glycero-D-galacto-2-nonulopyranosonate (8). An additional product of the condensation reaction was methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2,6-anhydro-3,5-dideoxy-D-glycero-D-galacto-non-2-enopyranosonate, which was obtained in 40% yield based on 8. O-Deacetylation of 13 and subsequent saponification gave benzyl 2-acetamido-2-deoxy-6-O-(potassium 5-acetamido-3,5-dideoxy-β-D-glycero-D-galacto-2-nonulopyranosylonate)-α-D-glucopyranosi de (16). Catalytic hydrogenolysis of 16 yielded the title product as its potassium salt.