Uses
2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl trichloroacetimidate, 98%(N) (2,3,4,6-Tetra-O-acetyl-&beta) can be used in glycobiology research.
Synthesis
1. (2R,3R,4S,5R,6R)-2-(Acetoxymethyl)-6-hydroxytetrahydro-2H-pyran-3,4,5-triyl triacetate (5 g, 12.8 mmol) was dissolved in DMF (60 mL) and hydrazine acetate (1.3 g, 14.1 mmol) was added. The reaction mixture was stirred at room temperature overnight and subsequently concentrated to dryness under reduced pressure. The residue was dissolved with EtOAc (200 mL) and washed sequentially with saturated aqueous NaHCO3 and deionized water. The organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by silica gel column chromatography (eluent: hexane-EtOAc, 1:1, v/v) afforded a white solid product (4.27 g, 96% yield).
2. The above product (2.1 g, 6.03 mmol), trichloroacetonitrile (12.1 mL, 121 mmol) and DCM (40 mL) were mixed and cooled to 0 °C. Cs2CO3 (1.96 g, 6.03 mmol) was added and stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure and purified by silica gel column chromatography (eluent: hexane-EtOAc, 2:1, v/v) to give white solid sialyl ester (2.85 g, 96% yield).
3. The sialyl ester (0.88 g, 1.62 mmol), acceptor (0.73 g, 1.1 mmol), molecular sieve MS-4A and DCM (40 mL) were mixed and stirred at room temperature for 30 min. After cooling to -70 °C, TfOH (29 μL, 0.32 mmol) was added. The reaction mixture was stirred at -70 to -20 °C for 1 h and quenched with Et3N (0.05 mL). The mixture was diluted with DCM (200 mL), washed sequentially with saturated aqueous NaHCO3 and deionized water, the organic phase was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. Purification by silica gel column chromatography (eluent: hexane-EtOAc, 3:2, v/v) gave a white solid disaccharide product (1.05 g, 95% yield).
The 1H-NMR (500 MHz, CDCl3) and 13C-NMR (75 MHz, CDCl3) data were consistent with the structure of the target compound.
References
[1] Organic and Biomolecular Chemistry, 2017, vol. 15, # 26, p. 5602 - 5608
[2] Tetrahedron Letters, 2005, vol. 46, # 14, p. 2445 - 2448
[3] Patent: WO2012/135049, 2012, A1. Location in patent: Page/Page column 58-59
[4] Chemistry - An Asian Journal, 2014, vol. 9, # 7, p. 1786 - 1796
[5] Chinese Chemical Letters, 2016, vol. 27, # 12, p. 1740 - 1744
