2023 Volume 81 Issue 7 Pages 692-705
The authors have been working 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 analogue molecules are not degraded by the glycoside hydrolases expressed in cells, and thus are expected to be useful molecular tools that maintain the original biological activity of carbohydrates at the cell level. However, their biological potentials are not well understood because quite limited number of pseudo-glycans have been synthesized. In this article, the author summarizes our recent report on the creation of C-glycoside analogues of ganglioside GM3. The author has devised the CHF-sialoside linkage to mimic the properties of the O-sialoside bond in the development of pseudo-GM3. Conformational analysis of the synthesized CHF-sialoside disaccharides confirmed that the expected conformational control by F-atom introduction was achieved, and furthermore, results suggesting that this contributed to the enhancement of biological activity were successfully obtained. In order to further validate the usefulness of the C-glycoside analogues, it is important to streamline the cumbersome synthesis process. The author proposed the direct C-glycosylation method using atom-transfer radical coupling, which was utilized to the synthesis of pseudo-isomaltose and pseudo-KRN7000.
