Synthesis of three regioisomers of the pentasaccharide part of the Skp1 glycoprotein of Dictyostelium discoideum

Three regioisomers of the linear pentasaccharide part of the Skp1 glycoprotein, found in Dictyostelium discoideum, were prepared in the form of (2-trimethylsilyl)ethyl glycosides by means of 2+3 block syntheses using the disaccharide donor at the non-reducing end, and three different trisaccharide acceptors at the reducing end. Fucosylation of (2-trimethylsilyl)ethyl 3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-NPhth-β-d-glucopyranoside with different fucosyl donors carrying an O-(2-naphthyl)methyl ether as a temporary-protecting group at positions C2, C3 or C4 gave rise to the protected core trisaccharides. After selective removal of the (2-naphthyl)methyl group, the resulting acceptors were glycosylated with the α(1→6) linked digalactosyl donor to yield the respective three regioisomeric pentasaccharides. Transformation of the phthalimido moiety into an N-acetyl group, followed by catalytic hydrogenation of the reducible-protecting groups furnished the free target pentasaccharides, which should be able to assist during the elucidation of the exact structure of the natural pentasaccharide.

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(2-Trimethylsilyl)ethyl 2-O-acetyl-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-d-glucopyranosideC55H61NO13Si[α]D = −6.1 (c 0.16, CHCl3)

(2-Trimethylsilyl)ethyl 3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-d-glucopyranosideC53H59NO12Si[α]D = −48.5 (c 0.24, CHCl3)

(2-Trimethylsilyl)ethyl 3,4-di-O-benzyl-2-O-(2-naphthyl)methyl-α-l-fucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-d-glucopyranosideC84H89NO16Si[α]D = −37.7 (c 0.13, CHCl3)

(2-Trimethylsilyl)ethyl 3,4-di-O-benzyl-α-l-fucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-d-glucopyranosideC73H81NO16Si[α]D = −47.4 (c 0.15, CHCl3)

(2-Trimethylsilyl)ethyl 2,4-di-O-benzyl-3-O-(2-naphthyl)methyl-α-l-fucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-d-glucopyranosideC84H89NO16Si[α]D = −33.8 (c 0.21, CHCl3)

(2-Trimethylsilyl)ethyl 2,4-di-O-benzyl-α-l-fucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-d-glucopyranosideC73H81NO16Si[α]D = −61.0 (c 0.12, CHCl3)

(2-Trimethylsilyl)ethyl-2,3-di-O-benzyl-4-O-(2-naphthyl)methyl-α-l-fucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-d-glucopyranosideC84H89NO16Si[α]D = −40.5 (c 0.22, CHCl3)

(2-Trimethylsilyl)ethyl 2,3-di-O-benzyl-α-l-fucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-d-glucopyranosideC73H81NO16Si[α]D = −34.2 (c 0.16, CHCl3)

Phenyl 3,4-O-isopropylidene-6-O-(methoxydimethyl)methyl-2-O-(2-naphthyl)methyl-1-thio-β-d-galactopyranosideC30H36O6S[α]D = +2.7 (c 1.01, CHCl3)

Phenyl 3,4-O-isopropylidene-2-O-(2-naphthyl)methyl-1-thio-β-d-galactopyranosideC26H28O5S[α]D = +12.8 (c 1.03, CHCl3)

Phenyl 2,3,4,6-tetra-O-benzyl-α/β-d-galactopyranosyl-(1→6)-3,4-O-isopropylidene-2-O-(2-naphthyl)methyl-1-thio-β-d-galactopyranosideC60H62O10S[α]D = +26.7 (c 1.05, CHCl3)

Phenyl 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-3,4-di-O-acetyl-2-O-(2-naphthyl)methyl-1-thio-β-d-galactopyranosideC61H62O12S[α]D = +28.2 (c 0.99, CHCl3)

(2-Trimethylsilyl)ethyl 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-3,4-di-O-acetyl-2-O-(2-naphthyl)methyl-α-d-galactopyranosyl-(1→2)-3,4-di-O-benzyl-α-l-fucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-d-glucopyranosideC128H137NO28Si[α]D = +64.8 (c 0.13, CHCl3)

(2-Trimethylsilyl)ethyl 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-3,4-di-O-acetyl-2-O-(2-naphthyl)methyl-α-d-galactopyranosyl-(1→3)-2,4-di-O-benzyl-α-l-fucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-d-glucopyranosideC128H137NO28Si[α]D = −23.6 (c 0.12, CHCl3)

(2-Trimethylsilyl)ethyl 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-3,4-di-O-acetyl-2-O-(2-naphthyl)methyl-α-d-galactopyranosyl-(1→4)-2,3-di-O-benzyl-α-l-fucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-4,6-O-benzylidene-2-deoxy-2-phthalimido-β-d-glucopyranosideC128H137NO28Si[α]D = −4.3 (c 0.14, CHCl3)

(2-Trimethylsilyl)ethyl 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-2-O-(2-naphthyl)methyl-α-d-galactopyranosyl-(1→2)-3,4-di-O-benzyl-α-l-fucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-2-acetamido-4,6-O-benzylidene-2-deoxy-β-d-glucopyranosideC118H133NO25Si[α]D = +6.8 (c 0.13, CHCl3)

(2-Trimethylsilyl)ethyl 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-2-O-(2-naphthyl)methyl-α-d-galactopyranosyl-(1→3)-2,4-di-O-benzyl-α-l-fucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-2-acetamido-4,6-O-benzylidene-2-deoxy-β-d-glucopyranosideC118H133NO25Si[α]D = −11.5 (c 0.15, CHCl3)

(2-Trimethylsilyl)ethyl 2,3,4,6-tetra-O-benzyl-α-d-galactopyranosyl-(1→6)-2-O-(2-naphthyl)methyl-α-d-galactopyranosyl-(1→4)-2,3-di-O-benzyl-α-l-fucopyranosyl-(1→2)-3,4,6-tri-O-benzyl-β-d-galactopyranosyl-(1→3)-2-acetamido-4,6-O-benzylidene-2-deoxy-β-d-glucopyranosideC118H133NO25Si[α]D = +5.8 (c 0.12, CHCl3)

(2-Trimethylsilyl)ethyl α-d-galactopyranosyl-(1→6)-α-d-galactopyranosyl-(1→2)-α-l-fucopyranosyl-(1→2)-β-d-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-β-d-glucopyranosideC37H67NO25Si[α]D = +29.7 (c 0.14, MeOH)

(2-Trimethylsilyl)ethyl α-d-galactopyranosyl-(1→6)-α-[-galactopyranosyl-(1→3)-α-l-fucopyranosyl-(1→2)-β-d-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-β-d-glucopyranosideC37H67NO25Si[α]D = +21.1 (c 0.18, MeOH)

(2-Trimethylsilyl)ethyl α-d-galactopyranosyl-(1→6)-α-d-galactopyranosyl-(1→4)-α-l-fucopyranosyl-(1→2)-β-d-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-β-d-glucopyranosideC37H67NO25Si[α]D = +22.6 (c 0.22, MeOH)