Hasegawa A, Kato M, Ando T, Ishida H, Kiso M
Department of Applied Bioorganic Chemistry, Gifu University, Japan.
Carbohydr Res. 1995 Sep 8;274:165-81. doi: 10.1016/0008-6215(95)00135-g.
Sialyl Le(x) ganglioside analogues containing 2-epi-, 2,3-di-epi-, 4-epi-, and 2-O-methyl-L-fucose in place of the L-fucose residue have been synthesized. Glycosylation of 2-(trimethylsilyl)ethyl O-(2-acetamido-4,6-O-benzylidene-2-deoxy-beta-D-glucopyranosyl)-(1-->3)- 2,4,6- tri-O-benzyl-beta-D-galactopyranoside with the methyl 1-thioglycoside derivatives of the respective fucose analogues, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the corresponding protected 2-(trimethylsilyl)ethyl deoxy-alpha-L-hexopyranosyl-(1-->3)-O-(2- acetamido-2-deoxy-beta-D-glucopyranosyl)-(1-->3)-beta-D-galactopyrano sid es. These were transformed by reductive ring-opening of their benzylidene acetal groups into the glycosyl acceptors. Dimethyl (methylthio)sulfonium triflate-promoted glycosylation of these compounds with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto -2- nonulopyranosylonate)-(2-->3)-2,4,6-tri-O-benzoyl-1-thio-beta-D- galactopyranoside afforded the desired pentasaccharides, which were converted via reductive removal of their benzyl groups, O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and reaction with trichloroacetonitrile, into the corresponding alpha-tri-chloroacetimidates. Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol these in the presence of boron trifluoride etherate afforded the expected beta-glycosides, which were transformed in good yields, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and deesterification, into the target gangliosides. The 2-(trimethylsilyl)ethyl glycosides of sialyl Le(x) oligosaccharides containing modified fucose were also prepared from the intermediates of the ganglioside synthesis.
已经合成了含有2-表位、2,3-二表位、4-表位和2-O-甲基-L-岩藻糖以取代L-岩藻糖残基的唾液酸化Le(x)神经节苷脂类似物。使用三氟甲磺酸二甲硫鎓盐（DMTST）作为促进剂，使2-(三甲基甲硅烷基)乙基O-(2-乙酰氨基-4,6-O-亚苄基-2-脱氧-β-D-吡喃葡萄糖基)-(1→3)-2,4,6-三-O-苄基-β-D-吡喃半乳糖苷与相应岩藻糖类似物的甲基硫代糖苷衍生物进行糖基化反应，得到相应的受保护的2-(三甲基甲硅烷基)乙基脱氧-α-L-己吡喃糖基-(1→3)-O-(2-乙酰氨基-2-脱氧-β-D-吡喃葡萄糖基)-(1→3)-β-D-吡喃半乳糖苷。通过其亚苄基缩醛基团的还原开环将这些化合物转化为糖基受体。这些化合物在三氟甲磺酸二甲硫鎓盐促进下与甲基O-(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-壬酮吡喃糖醛酸酯)-(2→3)-2,4,6-三-O-苯甲酰基-1-硫代-β-D-吡喃半乳糖苷进行糖基化反应，得到所需的五糖，通过还原除去其苄基、O-乙酰化、选择性除去2-(三甲基甲硅烷基)乙基基团以及与三氯乙腈反应，将其转化为相应的α-三氯乙亚胺酯。在三氟化硼乙醚存在下，(2S,3R,4E)-2-叠氮基-3-O-苯甲酰基-4-十八碳烯-1,3-二醇与这些化合物进行糖基化反应，得到预期的β-糖苷，通过选择性还原叠氮基、与十八烷酸偶联、O-脱酰基化和脱酯反应，以良好的产率将其转化为目标神经节苷脂。含有修饰岩藻糖的唾液酸化Le(x)寡糖的2-(三甲基甲硅烷基)乙基糖苷也由神经节苷脂合成的中间体制备。
