Systematic syntheses of influenza neuraminidase inhibitors: A series of carbosilane dendrimers uniformly functionalized with thioglycoside-type sialic acid moieties
Systematic syntheses of influenza neuraminidase inhibitors: A series of carbosilane dendrimers uniformly functionalized with thioglycoside-type sialic acid moieties
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DOI：
10.1016/j.bmc.2009.06.036
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发表时间：
2009-08-01
影响因子：
3.5
通讯作者：
Matsuoka, Koji
中科院分区：
文献类型：
--
作者：
Sakamoto, Jun-Ichi;Koyama, Tetsuo;Matsuoka, Koji
In order to develop novel influenza sialidase inhibitors, we constructed a library of glycoclusters composed of twelve types of sialylated dendrimers with thioglycosidic linkage that are resistant to hydrolysis by the sialidases. These sialodendrimers were synthesized by condensation reaction between a thiosialoside modified on the aglycon terminal end by a thioacetyl group and twelve types of carbosilane dendrimers having brominated terminal ends under deacetylation conditions, and temporal re-protection was performed for purification. Removal of all protection of the glycodendrimers was accomplished by transesterification and subsequent saponification to provide corresponding water-soluble glycodendrimers in good yields. For investigation of the structure-activity relationship, dendrimer scaffolds having differences in number of the sugar moieties, such as 3-, 4-, 6-and 12-functionalized dendrimers, and in linkage patterns, such as normal aliphatic linkage, ether-and amide-linkages. Biological evaluations of these glycodendrimers showed that all of the ether-and amide-elongated compounds had inhibitory potencies for the influenza sialidases in the mM range, while compounds having normal aliphatic linkage did not have any activities except for a 12-functionalized compound. (C) 2009 Elsevier Ltd. All rights reserved.
