Synthesis and Biological Evaluation of Non-Hydrolizable 1,2,3-Triazole Linked Sialic Acid Derivatives as Neuraminidase Inhibitors.
Synthesis and Biological Evaluation of Non-Hydrolizable 1,2,3-Triazole Linked Sialic Acid Derivatives as Neuraminidase Inhibitors.
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DOI：
10.1002/ejoc.200900117
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发表时间：
2009-06
影响因子：
2.8
通讯作者：
Linhardt RJ
中科院分区：
文献类型：
--
作者：
Weïwer M;Chen CC;Kemp MM;Linhardt RJ
以α-唾液酸叠氮化物1为底物，通过铜催化叠氮-炔基惠氏环加成反应(点击化学)有效地合成了唾液酸的1，2，3-三氮唑衍生物。我们的方法是生成非天然的唾液酸N-糖苷，这种糖苷对神经氨酸酶催化的水解具有抵抗力，而不是天然的O-糖苷。这些N-糖苷将作为神经氨酸酶抑制剂来阻止新病毒粒子的释放。作为初步研究，以71-89%的产率合成了1，2，3-三氮唑连接的唾液酸衍生物的小文库。以α-唾液酸叠氮化物1和C-8丙叉基唾液酸受体为原料，以68%的产率合成了模拟唾液酸的双糖。以丙烯酸化的季戊四醇为受体，合成了唾液酸包覆的树枝状大分子。这些新的唾液酸衍生物随后被评估为潜在的神经氨酸酶抑制剂；观察到微摩尔IC50值，与已知的唾液酸酶抑制剂Neu5Ac2en相当。
α-Sialic acid azide 1 has been used as a substrate for the efficient preparation of 1,2,3-triazole derivatives of sialic acid using the copper-catalyzed azide-alkyne Huisgen cycloaddition (“click chemistry”). Our approach is to generate non-natural N-glycosides of sialic acid that are resistant to neuraminidase catalyzed hydrolysis as opposed to the natural O-glycosides. These N-glycosides would act as neuraminidase inhibitors to prevent the release of new virions. As a preliminary study, a small library of 1,2,3-triazole-linked sialic acid derivatives has been synthesized in 71-89% yield. A disaccharide mimic of sialic acid has also been prepared using the α-sialic acid azide 1 and a C-8 propargyl sialic acid acceptor in 68% yield. A model sialic acid coated dendrimer was also synthesized from a per-propargylated pentaerythritol acceptor. These novel sialic acid derivatives were then evaluated as potential neuraminidase inhibitors using a 96-well plate fluorescence assay; micromolar IC50 values were observed, comparable to the known sialidase inhibitor Neu5Ac2en.
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影响因子：
168.9
作者：
Kiso, M;Mitamura, K;Kawaoka, Y
通讯作者：
Kawaoka, Y
影响因子：
2.7
作者：
Li, Jian;Zheng, Mingyue;Jiang, Hualiang
通讯作者：
Jiang, Hualiang
影响因子：
4.3
作者：
Papin, Caroline;Doisneau, Gilles;Beau, Jean-Marie
通讯作者：
Beau, Jean-Marie
影响因子：
5.4
作者：
Matrosovich, MN;Matrosovich, TY;Klenk, HD
通讯作者：
Klenk, HD
影响因子：
3.6
作者：
Kim, Jin-Hwan;Huang, Fei;Linhardt, Robert J.
通讯作者：
Linhardt, Robert J.