Suzuki Katsuhiko, Daikoku Shusaku, Son Sang-Hyun, Ito Yukishige, Kanie Osamu
ERATO, Japan Science and Technology Agency (JST), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
ERATO, Japan Science and Technology Agency (JST), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Synthetic Cellular Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Carbohydr Res. 2015 Apr 10;406:1-9. doi: 10.1016/j.carres.2014.12.010. Epub 2015 Jan 14.
Sialic acid derivatives, analogs, and their conjugates are expected to be pharmaceutical candidates such as anti-influenza drugs and also useful probes for investigating the biological role of glycoconjugates. Derivatives of 3-fluorinated sialic acid (3-F-Sia) have been found to be excellent probes in investigating functions and mechanisms of a series of proteins. Here, we describe the syntheses of 3-F-Sia derivatives, which are useful in making biologically important conjugate probes. A practical method for the construction of 3-fluorinated sialosides based on the stereoselective formation of the corresponding anomeric O-trimethylsilyl ether and their nucleophilic attack by an alkyl halide, an allyl halide in particular, was developed. In addition, details of the synthesis of cytidine monophosphate (CMP)-3-F-Sia bearing a fluorescent tag, which has been proven to show dual functions as a substrate of CMP-sialic acid transporter (CST) and an inhibitor of sialyltransferase (STase), are described.
唾液酸衍生物、类似物及其缀合物有望成为抗流感药物等药物候选物，也是研究糖缀合物生物学作用的有用探针。已发现3-氟唾液酸（3-F-Sia）衍生物是研究一系列蛋白质功能和机制的优秀探针。在此，我们描述了3-F-Sia衍生物的合成，其可用于制备具有生物学重要性的缀合物探针。开发了一种基于相应异头O-三甲基硅基醚的立体选择性形成及其被卤代烃（特别是烯丙基卤）亲核进攻来构建3-氟唾液酸苷的实用方法。此外，还描述了带有荧光标签的单磷酸胞苷（CMP）-3-F-Sia的合成细节，该化合物已被证明具有作为CMP-唾液酸转运蛋白（CST）底物和唾液酸转移酶（STase）抑制剂的双重功能。
