Iwayama Yuki, Ando Hiromune, Ishida Hideharu, Kiso Makoto
Department of Applied Bioorganic Chemistry, Faculty of Applied Biological Sciences, Gifu University, 1-1 Yanagido, Gifu-shi, Gifu, Japan.
Chemistry. 2009;15(18):4637-48. doi: 10.1002/chem.200802706.
A neuritegenic ganglioside from sea cucumber, HLG-2 (see figure), has been synthesized for the first time. The unique tandem of sialic acids, Neu5Gc-alpha(2,4)-NeuAc, was established by the combination of a reactive N-Troc sialyl donor and a 1,5-lactamized sialyl acceptor. The ceramide counterpart was assembled in a stereoselective manner. Direct connection of the trisaccharide and the ceramide successfully afforded a precursor of HLG-2, which was converted to ganglioside HLG-2 in pure form.A first synthesis of the neuritegenic ganglioside HLG-2, which was identified in extracts of the sea cucumber Holothuria leucospilota, is described. The characteristic sequence of the trisaccharide part, alpha-N-glycolylsialyl-(2,4)-alpha-N-acetylsialyl-(2,6)-glucoside, was efficiently assembled by coupling of a highly active N-2,2,2-trichloroethoxycarbonyl (Troc)-protected sialyl donor and a 1,5-lactamized sialyl acceptor with high stereoselectivity. The corresponding trisaccharyl imidate donor was directly glycosidated with the primary hydroxyl group of the ceramide part, producing protected HLG-2 in relatively high yield, global deprotection of which furnished ganglioside HLG-2 in highly pure form.
首次合成了一种来自海参的神经突生成神经节苷脂HLG-2（见图）。通过反应性N-三氯乙氧羰基（Troc）唾液酸供体和1,5-内酰胺化唾液酸受体的组合，确定了独特的唾液酸串联结构，即Neu5Gc-α(2,4)-NeuAc。神经酰胺部分以立体选择性方式组装。三糖和神经酰胺的直接连接成功得到了HLG-2的前体，该前体被转化为纯形式的神经节苷脂HLG-2。本文描述了首次合成在白色海参提取物中鉴定出的神经突生成神经节苷脂HLG-2。通过高活性N-2,2,2-三氯乙氧羰基（Troc）保护的唾液酸供体与1,5-内酰胺化唾液酸受体的高立体选择性偶联，高效组装了三糖部分的特征序列α-N-羟乙酰神经氨酸-(2,4)-α-N-乙酰神经氨酸-(2,6)-葡萄糖苷。相应的三糖基亚氨酸酯供体与神经酰胺部分的伯羟基直接进行糖基化反应，以相对较高的产率生成了保护型HLG-2，对其进行整体脱保护得到了高纯度的神经节苷脂HLG-2。
