Synthetic study of 3-fluorinated sialic acid derivatives.

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.