期刊
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
卷 2009, 期 16, 页码 2611-2620出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/ejoc.200900117
关键词
Sialic acids; Cycloaddition; N-Glycosides; Inhibitors; Viruses
资金
- NIAID NIH HHS [R01 AI065786] Funding Source: Medline
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI065786] Funding Source: NIH RePORTER
alpha-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 nonnatural 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 alpha-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 perpropargylated 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. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
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