[带有寡糖GM1和去唾液酸GM1神经节苷脂链的氨乙基糖苷的合成]
[Synthesis of aminoethylglycosides with oligosaccharide GM1 and asialo-GM1 ganglioside chains].
作者信息
Cheshev P E, Khatuntseva E A, Tsvetkov Iu E, Shashkov A S, Nifant'ev N E
机构信息
Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninskii pr. 47, Moscow, 119991 Russia.
出版信息
Bioorg Khim. 2004 Jan-Feb;30(1):68-79. doi: 10.1023/b:rubi.0000015775.24385.a0.
4'-O-Glycosylation of 2-azidoethyl 2,3,6-tri-O-benzyl-4-O-(2,3-di-O- benzyl-6-O-benzoyl-beta-D-galactopyranosyl)-beta-D-glucopyranoside with a disaccharide donor, 4-trichloroacetamidophenyl 4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-beta-D- galactopyranosyl)-1-thio-2-trichloroacetamido-beta-D-galactopyranoside, in dichloromethane in the presence of N-iodosuccinimide and trifluoromethanesulfonic acid resulted in a tetrasaccharide, 2-azidoethyl (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-(1-->3)- (4,6-di-O-acetyl-2-deoxy-2-trichloroacetamido-beta-D-galactopyranosyl)- (1-->4)-(2,3-di-O-benzyl-6-O-benzoyl-beta-D-galactopyranosyl)- (1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside, in 69% yield. The complete removal of O-protecting groups in the tetrasaccharide, the replacement of N-trichloroacetyl by N-acetyl group, and the reduction of the aglycone azide group to amine led to the target aminoethyl glycoside of beta-D-Gal- (1-->3)-beta-D-GalNAc-(1-->4)-beta-D-Gal-(1-->4)-beta-D-Glc-OCH2CH2NH2 containing the oligosaccharide chain of asialo-GM1 ganglioside in 72% overall yield. Selective 3'-O-glycosylation of 2-azidoethyl 2,3,6-tri-O- benzyl-4-O-(2,6-di-O-benzyl-beta-D-galactopyranosyl)-beta-D-glucopyranoside with thioglycoside methyl (ethyl 5-acetamido-4,7,8,9-tetra-O- acetyl-3,5-dideoxy-2-thio-D-glycero-alpha-D-galacto-2-nonulopyranosyl)oate in acetonitrile in the presence of N-iodosuccinimide and trifluoroacetic acid afforded 2-azidoethyl [methyl (5-acetamido-4,7,8,9-tetra-O-acetyl- 3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosyl)oate in acetonitrile in the presence of N-iodosuccinimide and tri-fluoracetic acid afforded 2-azidoethyl[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl- 3,5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosyl) (2,6-di-O-benzyl-beta-D-galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D- glucopyranoside, the selectively protected derivative of the oligosaccharide chain of GM3 ganglioside, in 79% yield. Its 4'-O-glycosylation with a disaccharide glycosyl donor, (4-trichloroacetophenyl-4,6-di-O-acetyl-2-deoxy-3-O-(2,3,4,6-tetra-O- acetyl-beta-D-galactopyranosyl) 1-thio-2-trichloroacetamido-beta-D-galactopyranoside in dichloromethane in the presence of N-iodosuccinimide and trifluoroacetic acid gave 2-azidoethyl (2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)- (1-->3)-(4,6-di-O-acetyl-2-deoxy-2-trichloroacetamido-beta-D- galactopyranosyl)-(1-->4)-[[methyl (5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D- galacto-2-nonulopyranosyl)onate]-(2-->3)]-(2,6-di-O-benzyl-beta-D- galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzyl-beta-D-glucopyranoside in 85% yield. The resulting pentasaccharide was O-deprotected, its N-trichloroacetyl group was replaced by N-acetyl group, and the aglycone azide group was reduced to afford in 85% overall yield aminoethyl glycoside of beta-D-Gal-(1-->3)-beta-D-GalNAc-(1-->4)-[alpha-D-Neu5Ac-(2-->3)]- beta-D-Gal-(1-->4)-beta-D-Glc-OCH2CH2NH2 containing the oligosaccharide chain of GM1 ganglioside. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.
2-叠氮基乙基 2,3,6-三-O-苄基-4-O-(2,3-二-O-苄基-6-O-苯甲酰基-β-D-吡喃半乳糖基)-β-D-吡喃葡萄糖苷与二糖供体 4-三氯乙酰氨基苯基 4,6-二-O-乙酰基-2-脱氧-3-O-(2,3,4,6-四-O-乙酰基-β-D-吡喃半乳糖基)-1-硫代-2-三氯乙酰氨基-β-D-吡喃半乳糖苷在二氯甲烷中，于 N-碘代琥珀酰亚胺和三氟甲磺酸存在下进行 4'-O-糖基化反应，得到四糖 2-叠氮基乙基 (2,3,4,6-四-O-乙酰基-β-D-吡喃半乳糖基)-(1→3)-(4,6-二-O-乙酰基-2-脱氧-2-三氯乙酰氨基-β-D-吡喃半乳糖基)-(1→4)-(2,3-二-O-苄基-6-O-苯甲酰基-β-D-吡喃半乳糖基)-(1→4)-2,3,6-三-O-苄基-β-D-吡喃葡萄糖苷，产率为 69%。四糖中 O-保护基团的完全去除、N-三氯乙酰基被 N-乙酰基取代以及苷元叠氮基团还原为胺，以 72%的总产率得到了含有脱唾液酸 GM1 神经节苷脂寡糖链的目标β-D-半乳糖-(1→3)-β-D-氨基半乳糖-(1→4)-β-D-半乳糖-(1→4)-β-D-葡萄糖-OCH2CHsNH2 的氨基乙基糖苷。2-叠氮基乙基 2,3,6-三-O-苄基-4-O-(2,6-二-O-苄基-β-D-吡喃半乳糖基)-β-D-吡喃葡萄糖苷与硫代糖苷甲基 (乙基 5-乙酰氨基-4,7,8,9-四-O-乙酰基-3,5-二脱氧-2-硫代-D-甘油-α-D-半乳糖-2-壬吡喃糖基) 酯在乙腈中，于 N-碘代琥珀酰亚胺和三氟乙酸存在下进行选择性 3'-O-糖基化反应，得到 2-叠氮基乙基 [甲基 (5-乙酰氨基-4,7,8,9-四-O-乙酰基-3,5-二脱氧-D-甘油-α-D-半乳糖-2-壬吡喃糖基) (2,6-二-O-苄基-β-D-吡喃半乳糖基)-(1→4)-2,3,6-三-O-苄基-β-D-吡喃葡萄糖苷，即 GM3 神经节苷脂寡糖链的选择性保护衍生物，产率为 79%。其与二糖糖基供体 (4-三氯乙酰苯基-4,6-二-O-乙酰基-2-脱氧-3-O-(2,3,4,6-四-O-乙酰基-β-D-吡喃半乳糖基) 1-硫代-2-三氯乙酰氨基-β-D-吡喃半乳糖苷在二氯甲烷中，于 N-碘代琥珀酰亚胺和三氟乙酸存在下进行 4'-O-糖基化反应，得到 2-叠氮基乙基 (2,3,4,6-四-O-乙酰基-β-D-吡喃半乳糖基)-(1→3)-(4,6-二-O-乙酰基-2-脱氧-2-三氯乙酰氨基-β-D-吡喃半乳糖基)-(1→4)-[[甲基 (5-乙酰氨基-4,7,8,9-四-O-乙酰基-3,5-二脱氧-D-甘油-α-D-半乳糖-2-壬吡喃糖基) 酯]-(2→3)]-(2,6-二-O-苄基-β-D-吡喃半乳糖基)-(1→4)-2,3,6-三-O-苄基-β-D-吡喃葡萄糖苷，产率为 85%。所得五糖进行 O-脱保护，其 N-三氯乙酰基被 N-乙酰基取代，苷元叠氮基团被还原，以 85%的总产率得到含有 GM1 神经节苷脂寡糖链的β-D-半乳糖-(1→3)-β-D-氨基半乳糖-(1→4)-[α-D-唾液酸-(2→)3]-β-D-半乳糖-(1→4)-β-D-葡萄糖-OCH2CH2NH2 的氨基乙基糖苷。该论文的英文版本：《俄罗斯生物有机化学杂志》，2004 年，第 30 卷，第 1 期；另见 http://www.maik.ru 。
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