Synthetic study of 3-fluorinated sialic acid derivatives

Katsuhiko Suzuki; Shusaku Daikoku; Sang-Hyun Son; Yukishige Ito; Osamu Kanie

doi:10.1016/j.carres.2014.12.010

Synthetic study of 3-fluorinated sialic acid derivatives

Carbohydr Res. 2015 Apr 10:406:1-9. doi: 10.1016/j.carres.2014.12.010. Epub 2015 Jan 14.

Authors

Katsuhiko Suzuki¹, Shusaku Daikoku¹, Sang-Hyun Son¹, Yukishige Ito², Osamu Kanie³

Affiliations

¹ ERATO, Japan Science and Technology Agency (JST), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
² 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.
³ ERATO, Japan Science and Technology Agency (JST), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Institute of Glycoscience, Tokai University, 4-1-1 Kitakaname, Hiratsuka, Kanagawa 259-1292, Japan. Electronic address: kanie@tokai-u.jp.

PMID: 25658060
DOI: 10.1016/j.carres.2014.12.010

Abstract

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.

Keywords: Alkylation; Glycosides; Inhibitor; Substrate.

MeSH terms

Enzyme Inhibitors / chemical synthesis
Fluorescent Dyes / chemical synthesis
Hydrocarbons, Fluorinated / chemical synthesis*
Molecular Probes / chemical synthesis*
Sialic Acids / chemical synthesis*
Sialyltransferases / antagonists & inhibitors
Stereoisomerism

Substances

Enzyme Inhibitors
Fluorescent Dyes
Hydrocarbons, Fluorinated
Molecular Probes
Sialic Acids
Sialyltransferases