Copyright Notice
Licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 Unported license. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Bookshelf ID: NBK593940PMID: 37590677
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Nishihara S, Angata K, Aoki-Kinoshita KF, et al., editors. Glycoscience Protocols (GlycoPODv2) [Internet]. Saitama (JP): Japan Consortium for Glycobiology and Glycotechnology; 2021-.
Introduction
Glycosyl fluorides are widely used for O- and C-glycosidation reactions. An advantage of the glycosyl fluoride as a glycosyl donor is its chemical stability due to the strong C–F bond compared with other corresponding glycosyl halides. The C–F bond can be efficiently cleaved with specific activating reagents to generate the reactive oxocarbenium intermediate (1). Glycosyl fluorides can be derived from thioglycoside (Figure 1), lactol (hemiacetal), acetate, methyl glycoside, epoxide, glycal, etc. (1,2).
Protocol
Here, the protocol for the synthesis of a glycosyl fluoride from the corresponding thioglycoside in the presence of DAST and NBS (Note 1) is described (3,4).
Materials
- 1.
Fully protected thioglycoside
- 2.
(Diethylamino)sulfur trifluoride (DAST)
- 3.
N-Bromosuccinimide (NBS)
- 4.
Dry dichloromethane
- 5.
Saturated aqueous NaHCO3
- 6.
Brine
- 7.
Na2SO4 (or MgSO4)
- 8.
Thin-layer chromatography (TLC) plate
- 9.
SiO2
Instruments
- 1.
Flask, magnetic stirrer, and stir bar (for reaction)
- 2.
Rotary evaporator
- 3.
Cooling bath (for synthesis)
- 4.
Separating funnel, funnel, and Erlenmeyer flask
- 5.
Chromatography tube for silica gel chromatography (for purification)
- 6.
Diaphragm pump (for filtration under reduced pressure, and concentration)
- 7.
Vacuum pump (for drying up)
Methods
- 1.
Protocol for synthesizing glycosyl fluoride from thioglycoside
- a.
Dissolve thioglycoside (1.0 equiv.) in CH2Cl2 (10 mL/mmol) under Ar.
- b.
Add DAST (1.5 equiv.) to the solution at −15°C.
- c.
Stir the reaction mixture for 2 min at −15°C.
- d.
Add NBS (1.3 equiv.) to the solution at −15°C.
- e.
Stir the reaction mixture at −15°C until the starting material is completely consumed as the progress of the reaction is monitored by TLC.
- f.
Dilute the mixture with CH2Cl2.
- g.
Quench the reaction by adding ice-cooled sat. aq. NaHCO3.
- h.
Wash the organic layer with brine.
- i.
Dry the organic layer over Na2SO4 (or MgSO4), filter the solution, and concentrate under reduced pressure.
- j.
Purify the residue by silica gel column chromatography to get the desired product.
Note
- 1.
The use of DAST-NBS system often produces glycosyl bromide as a byproduct and is limited because NBS reacts with olefinic functionality in the compound and protecting groups. To resolve these issues, an improved method for synthesizing glycosyl fluorides from thioglycosides without NBS has been developed (5).
References
- 1.
- Toshima K. Glycosyl fluorides in glycosidations. Carbohydr Res. 2000 July 10;327(1-2):15–26. [PubMed: 10968674] [CrossRef]
- 2.
- Mukaiyama T, Jona H. Glycosyl fluoride: A superb glycosyl donor in glycosyation. Proc Japan Acad, Ser. B. 2002 April 12;78(4):73–83. [CrossRef]
- 3.
- Nicolaou KC, Dolle RE, Papahatjis DP., Randall JL. Practical synthesis of oligosaccharide. Partial synthesis of avermectin B1a. J Am Chem Soc. 1984 July 1;106(15):4189–92. [CrossRef]
- 4.
- Imamura A, Ando H, Ishida H, Kiso M. Ganglioside GQ1b: Efficient total synthesis and the expansion to synthetic derivatives to elucidate its biological roles. 2009 April 17;74(8):3009-23. doi: 10.1021/jo8027888. PMID: 19296672. [PubMed: 19296672] [CrossRef]
- 5.
- Suzuki K, Ito Y, Kanie O. An improved method for the synthesis of protected glycosyl fluorides from thioglycosides using N,N-diethylaminosulfur trifluoride (DAST). Carbohydr Res. 2012 Oct 1;359:81–91. [PubMed: 22925769] [CrossRef]
Footnotes
The authors declare no competing or financial interests.
Figures
Figure 1:
Conversion of thioglycoside into glycosyl fluoride.