人类自然杀伤标志物抗原（HNK-1）是一类广泛存在于人类自然杀伤细胞和诸多粘附因子中的寡糖抗原结构，与细胞识别、粘附、迁移以及神经元的分化、生长等过程紧密相关。此外，HNK-1寡糖还影响恶性肿瘤及自身免疫性神经疾病的发生和发展。为了更好地研究HNK-1寡糖结构在生理、病理过程中的作用，本项目拟发展一条通用而又高效快速的合成策略来组装HNK-1系列相关寡糖：（1）通过理性设计获得正交保护的葡萄糖醛酸供体，使其既能够保证糖基供体的反应活性，又可以在寡糖骨架组装完成后实现选择性地脱保护，以便后期在特定羟基位点进行硫酸化操作。（2）发展以硝基糖烯为中间体的新方法来制备HNK-1的重要结构单元—乳糖胺模块。（3）筛选和优化活化体系，以基于“预活化”的一釜合成策略实现HNK-1系列寡糖及其衍生物的高效合成，并研究其与受体相互作用的构效关系。

The human natural killer-1 (HNK-1) glyco-epitope is an important carbohydrate component of glycoproteins and glycolipids involved in cell-cell and cell-substrate interactions, cell migration and neurite outgrowth. Moreover, it was found that the expression of HNK-1 epitopes is positively correlated with fatal tumor disease and autoimmune-based peripheral neuropathies. To investigate these processes, it is necessary to have access to homogenous and structurally defined HNK-1 epitope related oligosaccharides and derivatives. This proposal aims to develop a practical method for the synthesis of these important molecules and study the molecular recognition of the HNK-1 oligosaccharides and derivatives. The proposal has two specific aims. Specific Aim 1 is to develop a general strategy for the synthesis of natural HNK-1 oligosaccharides and HNK-1 derivatives. This research plans to use the 2-naphthylmethyl (2-NAP), benzoyl (Bz), 2-tert-butyldimethylsilyl (TBS) and benzyl (Bn) group as orthogonal protecting group in the synthesis. In this regard, these electron-donating protecting groups will arm the glucuronic acid donor; and the final deprotection could be achieved selectively to access the sulfonation. Meanwhile, 2-nitroglycal will be used to prepare 2-nitrothiolactoside as the key building block, constituting the lactosamine component in these oligosaccharides. And the strategy of preactivation-based one-pot oligosaccharide assembly will be applied to construct these oligosaccharides with 2-toluenethiol as leaving groups. Specific Aim 2 is to study the structure-activity relationships of the HNK-1 oligosaccharides with their different receptors.