[糖脂Gb3、Gb4和Gb5碳水化合物链的氨乙基糖苷的合成]

[Synthesis of aminoethyl glycosides of the carbohydrate chains of glycolipids Gb3, Gb4 i Gb5].

作者信息

Cheshev P E, Khatuntseva E A, Gerbst A G, 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. 2003 Jul-Aug;29(4):408-18. doi: 10.1023/a:1024905419008.

DOI:10.1023/a:1024905419008

PMID:12947763

Abstract

4-O-Glycosylation of 2-azidoethyl 2,3,6-tri-O-benzoyl-4-O-(2,3,6-tri-O-benzoyl-beta-D-galactopyranosyl)-beta- D-glucopyranoside with ethyl 2,3,4,6-tetra-O-benzyl- and ethyl 3-O-acetyl-2,4,6-tri-O-benzyl-1-thio-alpha-D-galactopyranoside in the presence of methyl trifluoromethanesulfonate led to trisaccharide 2-azidoethyl (2,3,4,6-tetra-O-benzyl-alpha-D-galactopyranosyl)-(1-->4)- (2,3,6-tri-O-benzoyl-beta-D-galactopyranosyl)-(1-->4)2,3,6-tri-O- benzoyl-beta-D-glucopyranoside and its 3"-O-acetylated analogue, 2-azidoethyl (3-O-acetyl-2,4,6-tri-O-benzyl- alpha-D-galactopyranosyl)-(1-->4)-(2,3,6-tri-O-benzoyl-beta-D- galactopyranosyl)-(1-->4)-2,3,6-tri-O-benzoyl-beta-D-glucopyranoside, in yields of 85 and 83%, respectively. Deacetylation of the latter compound and subsequent glycosylation with 4-trichloroacetamidophenyl 3,4,6-tri-O-acetyl-2-deoxy-1-thio-2-trichloroacetamido-beta-D- galactopyranoside and 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 the corresponding selectively protected derivatives of tetrasaccharide GalNAc(beta 1-->3)Gal(alpha 1-->4)Gal(beta 1-->4)Glc beta-OCH2CH2N3 and pentasaccharide Gal(beta 1-->3)GalNAc(beta 1-->3)Gal(alpha 1-->4)Gal(beta 1-->4)Glc beta-OCH2CH2N3 in 88 and 73% yields, respectively. Removal of O-protecting groups, substitution of acetyl group for N-trichloroacetyl group, and reduction of the aglycone azide group resulted in the target 2-aminoethyl globo-tri-, -tetra-, and -pentasaccharide, respectively.

摘要

在三氟甲磺酸甲酯存在下，2-叠氮基乙基 2,3,6-三-O-苯甲酰基-4-O-(2,3,6-三-O-苯甲酰基-β-D-吡喃半乳糖基)-β-D-吡喃葡萄糖苷与 2,3,4,6-四-O-苄基乙基和 3-O-乙酰基-2,4,6-三-O-苄基-1-硫代-α-D-吡喃半乳糖苷进行 4-O-糖基化反应，得到三糖 2-叠氮基乙基(2,3,4,6-四-O-苄基-α-D-吡喃半乳糖基)-(1→4)-(2,3,6-三-O-苯甲酰基-β-D-吡喃半乳糖基)-(1→4)2,3,6-三-O-苯甲酰基-β-D-吡喃葡萄糖苷及其 3''-O-乙酰化类似物 2-叠氮基乙基(3-O-乙酰基-2,4,6-三-O-苄基-α-D-吡喃半乳糖基)-(1→4)-(2,3,6-三-O-苯甲酰基-β-D-吡喃半乳糖基)-(1→4)-2,3,6-三-O-苯甲酰基-β-D-吡喃葡萄糖苷，产率分别为 85%和 83%。后一种化合物脱乙酰基，随后在 N-碘代琥珀酰亚胺和三氟甲磺酸存在下，于二氯甲烷中与 4-三氯乙酰氨基苯基 3,4,6-三-O-乙酰基-2-脱氧-1-硫代-2-三氯乙酰氨基-β-D-吡喃半乳糖苷和 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-吡喃半乳糖苷进行糖基化反应，分别以 88%和 73%的产率得到相应的四糖 GalNAc(β1→3)Gal(α1→4)Gal(β1→4)Glcβ-OCH2CH2N3 和五糖 Gal(β1→3)GalNAc(β1→3)Gal(α1→4)Gal(β1→4)Glcβ-OCH2CH2N3 的选择性保护衍生物。去除 O-保护基，用乙酰基取代 N-三氯乙酰基，并还原苷元叠氮基，分别得到目标 2-氨基乙基球三糖、球四糖和球五糖。