Sialic acids on the non-reducing terminus of sialylgylcans are abundantly expressed on the surface of mammalian cells. They play vital roles in cell-cell interactions and during infection by pathogenic bacteria and viruses. The chemical synthesis of sialylated glycans has been investigated for more than two decades, and interesting chemistry has been developed for coupling of sialic acid in an α-selective manner. Chemoenzymatic approaches are also now available for stereoselective sialylations. This mini-review focuses on very recent advances in stereoselective chemical sialylations and synthesis of natural sialylglycans using novel strategies, especially for the synthesis of the oligo/polysialic acid structure.
We describe L-O-rhamnosylation and D-O-glucosylation reactions using glycosyl donors in which the pyranose rings were restricted in a conformation that possessed more axial substituents. We call this conformation the axial-rich form. Introduction of the bulky silyl-protecting groups onto the adjacent trans-diols on the sugars restricted the conformation to the axial-rich form. The axial-rich L-rhamnosyl donor provided the b-isomer preferentially in the glycosylation reaction when trichloroacetimidate was adopted as the leaving group; however, the α/β ratio was only 1/4. This value was insufficient for practical applications. By contrast, the axial-rich glucosyl donor induced a highly β-selective reaction in which the anomeric α/β ratio was up to 2/98. In this case, the axial-rich skew-boat conformation of the pyranose ring was the key to successful stereoselective glycosylation. This method is an alternative for construction of the β-O-glucosidic linkages without relying upon participation of neighboring groups, a method that has long been employed. The new method was particularly effective for the synthesis of 2-O-glycosylated β-O-glucosides, for which direct construction using the neighboring group participation method is difficult.
Many bacterial, fungal, parasitical and plant species produce glycans containing O-furanoside linkages. These glycoconjugates are often essential for the viability of the organisms that produce them, and an increasing amount of work focused on their chemical synthesis has been carried out in recent years. However, despite these advances, compared to the synthesis of pyranose glycosides, this area has been poorly investigated. In this review we highlight the challenges inherent in the synthesis of furanose glycosides, summarize achievements in the field and suggest directions for future work.