Pre-activation-based one-pot synthesis of an α-(2,3)-sialylated core-fucosylated complex type Bi-antennary N-glycan dodecasaccharide
Pre-activation-based one-pot synthesis of an α-(2,3)-sialylated core-fucosylated complex type Bi-antennary N-glycan dodecasaccharide
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DOI：
10.1002/chem.200800757
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发表时间：
2008-01-01
影响因子：
4.3
通讯作者：
Huang, Xuefei
中科院分区：
文献类型：
--
作者：
Sun, Bin;Srinivasan, Balasubramanian;Huang, Xuefei
N-聚糖的合成由于其重要的生物学性质而受到高度关注。本文提出了一种基于预活化的高效收敛策略的复合型核心岩藻糖基化双触角N-聚糖十二糖的组装方法。逆合成这个极具挑战性的目标被分解为三个模块：唾液酸二糖，葡糖胺构建块和六糖二醇受体。在硫代半乳糖苷受体的存在下，通过选择性活化新的5-N-三氯乙酰基保护的唾液酸供体容易地获得唾液酸二糖。六糖二醇模块通过岩藻糖基化四糖受体的双甘露糖基化产生，岩藻糖基化四糖受体又通过岩藻糖基化二糖与含β-甘露糖的二糖供体的糖基化产生。三个模块的结合在一锅中进行，以高产率得到完全保护的十二糖。该合成方法的特点是对寡糖中间体进行了最少的保护基和糖苷配基调整，从而大大提高了整体合成效率。该策略的模块化特征表明该方法可以容易地适应于各种N-聚糖结构的合成。
Synthesis of N-glycans is of high current interests due to their important biological properties. A highly efficient convergent strategy based oil the pre-activation method for assembly of the complex type core fucosylated bi-antennary N-glycan dodecasaccharide has been developed. Retrosynthetically this extremely challenging target is broken down to three modules: a sialyl disaccharide, a glucosamine building block and a hexasaccharide diol acceptor. The sialyl disaccharide was easily obtained by selective activation of a new 5-N-trichloroacetyl protected sialyl donor in the presence of a thiogalactoside acceptor. The hexasaccharide diol module was produced by double mannosylation of a fucosylated tetrasaccharide acceptor, which in turn was generated by glycosylation of a fucosylated disaccharide with a beta-mannose containing disaccharide donor. The union of the three modules was performed in one-pot giving the fully protected dodecasaccharide in high yield. This synthesis is characterized by minimum protective group and aglycon adjustment on oligosaccharide intermediates, thus greatly enhancing the overall synthetic efficiency. The modular feature of this strategy Suggests that this method can be readily adapted to the synthesis of a wide variety of N-glycan structures.