Pseudo-glycoconjugates with a C-glycoside linkage.

Abstract

Work by the author and colleagues has been focused on the development of pseudo-glycans (pseudo-glycoconjugates), in which the O-glycosidic linkage of the natural-type glycan structure is replaced by a C-glycosidic linkage. These analogs are not degraded by cellular glycoside hydrolases and are thus expected to be useful molecular tools that may maintain the original biological activity for a long period in the cell. However, their biological potential is not yet well understood because only a few pseudo glycans have so far been synthesized. This article aims to provide a bird's-eye view of our recent studies on the creation of C-glycoside analogs of ganglioside GM3 based on the CHF-sialoside linkage, and summarizes the chemical insights acquired during our stereoselective synthesis of the C-sialoside bond, ultimately leading to pseudo-GM3. Conformational analysis of the synthesized CHF-sialoside disaccharides confirmed that the anticipated conformational control by F-atom introduction was successful, and furthermore, enhanced the biological activity. In order to improve access to C-glycoside analogs based on pseudo-GM3, it is still important to streamline the synthesis process. With this in mind, we designed and developed a direct C-glycosylation method using atom-transfer radical coupling, and employed it in syntheses of pseudo-isomaltose and pseudo-KRN7000.