Recent Strategies for Stereoselective Sialylation and Their Application to the Synthesis of Oligosialosides

Abstract

S i a l i c a c i d s o n t h e n o n -r e d u c i n g t e r m i n u s o f 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.

Chemoenzymatic synthesis of mono- and di-fluorinated Thomsen–Friedenreich (T) antigens and their sialylated derivatives

“…28–30 Due to the additional synthetic challenge of fluorinated oligosaccharides, only a few fluorinated sialosides have been synthesized. 31–33 The chemoenzymatic method developed here presents an efficient approach to access these challenging and biologically useful carbohydrate antigens.…”

Synthetic approach toward complexity of sialic acid-containing glycans

“…[8][9][10][11] Sialyl donors used in the reliable methods are fine-tuned for stereoselectivity and high-yield glycosylation via structural modifications. We have developed an N-Troc-sialyl donor, which offers high-yield glycosylation and high stereoselectivity, using various glycosyl acceptors and stereo-directing assistance with a nitrile solvent.…”

Extending the Glucosyl Ceramide Cassette Approach: Application in the Total Synthesis of Ganglioside GalNAc-GM1b

“…The crude residue obtained was purified by silica gel column chromatography (1:3 diethylether-n-hexane) to give 7 (28 mg, 96%). (8). To a solution of 5 (47 mg, 69.2 µmol) in CH 2 Cl 2 (1.4 mL) were added dimethylmalonyl dichloride (92 µL, 692 µmol) and triethylamine (96 µL, 692 µmol) at 0 °C.…”

“…Many synthetic organic chemists have contributed to developing methodology for the total synthesis of natural gangliosides and encountered several notable synthetic challenges, including regio-and stereo-selective sialylation and the introduction of the ceramide moiety into the oligosaccharide chain. Reliable methods for α-sialylation have been developed and used in numerous syntheses of natural gangliosides and analogues [7][8][9]; however, linking the flexible ceramide moiety to a large glycan remains a challenging undertaking. The typical procedure for connecting the lipid and glycan units is first to prepare the entire oligosaccharide framework and then to link it either to 2-azide sphingosine, which serves as a ceramide precursor, or to the ceramide moiety directly.…”