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 hexasaccharide in a completely protected form was accomplished for the first time. The L-threonine conjugate, N-(9-fluorenylmethoxycarbonyl)-O-[(5-acetamido-4,7,8,9-tetra-O-ben zyl-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylonic acid)-(2-->3)-(2,6-di-O-benzyl-beta-D-galactopyranosyl)-(1-->4)-2-acetam ido-2-deoxy-3,6-di-O-benzyl-beta-D-glucopyranosyl-(1-->6)-[(5-acetamido- 4,7,8,9-tetra-O-benzyl-3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulo pyranosylonic acid)-(2-->3)-2,6-di-O-benzyl-beta-D-galactopyranosyl-(1-->3)]-2-acetami do-2-deoxy-alpha-D-galactopyranosyl-(1d-->4c:1f-->4e)-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-gluco pyranose, N-(9-fluorenylmethoxycarbonyl)-O-(2-azido-6-O-t-butyldimethylsilyl -2-deoxy-alpha-D-galactopyranosyl)-L-threonine allyl ester, 8, 9 and N-(9-fluorenylmethoxycarbonyl)-O-(2-azido-4,6-O-benzylidene-3-O-ch loroacetyl-2-deoxy-alpha-D-galactopyranosyl)-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 as to obtain an alpha-glycosidic linkage without participation from the C-2 substituent. The threonine was attached to the sugar unit at the monosaccharide 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.
Singh
L
L
The Institute of Physical and Chemical Research (RIKEN), Saitama, Japan.
Nakahara
Y
Y
Ito
Y
Y
Nakahara
Y
Y
D015703:Antigens, CD; D002240:Carbohydrate Sequence; D006023:Glycoproteins / Q000737:chemistry; D006801:Humans; D051917:Leukosialin; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000737:chemistry; D011134:Polysaccharides / Q000138:chemical synthesis; D012795:Sialoglycoproteins / Q000737:chemistry*; D013601:T-Lymphocytes / Q000378:metabolism*; D013912:Threonine / Q000138:chemical synthesis*
D015703:Antigens, CD; D006023:Glycoproteins; D051917:Leukosialin; D011134:Polysaccharides; C465014:SPN protein, human; D012795:Sialoglycoproteins; D013912:Threonine; D019158:N-Acetylneuraminic Acid