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Nishihara S, Angata K, Aoki-Kinoshita KF, et al., editors. Glycoscience Protocols (GlycoPODv2) [Internet]. Saitama (JP): Japan Consortium for Glycobiology and Glycotechnology; 2021-.
Introduction
Carbohydrate units contain multiple hydroxy groups. Protection strategy is important for regio- and stereoselective glycan synthesis. Cyclic acetal groups are normally used for 1,2- or 1,3-diol protection. Among these protecting groups, benzylidene group is the most used protective group for 4,6-diols (Figure 1) (1). By appropriately choosing the reductive benzylidene cleavage reaction conditions, 4-O-benzyl-protected or 6-O-benzyl-protected glycosides can be obtained, respectively.
Figure 1:
The preparation of benzylidene acetal.
In the typical procedures, 10-camphorsulfonic acid (CSA) or p-toluenesulfonic acid (TsOH) are normally used as acid catalysts in N,N-dimethylformamide or acetonitrile. By these catalysts, the reaction period requires more than several hours. Cu(OTf)2 is a remarkable, efficient catalyst for benzylidene acetal preparation (2). The reaction proceeds at room temperature and completes within 1 h.
Protocol
The protocol for an efficient method for benzylidene acetal from diol using Cu(OTf)2 is described. This method is rapid and the isolation of product is normally easy. In a classical protocol, CSA or p-toluenesulfonic acid is typically used as an acid catalyst (Note 1).
Materials
- 1.
Substrate diol
- 2.
Benzaldehyde dimethyl acetal
- 3.
Cu(OTf)2
- 4.
Acetonitrile
- 5.
Thin-layer chromatography (TLC) plate
- 6.
Silica gel for purification
Instruments
- 1.
Magnetic stirrer
- 2.
Stirring bar
- 3.
Rotary evaporator
- 4.
Vacuum pump
- 5.
Ultrasonic device
Methods
- 1.
Add acetonitrile to substrate diol (1 mmol/10 mL).
- a.
When the diol is not soluble, sonication during the reaction is useful.
- 2.
Add benzaldehyde dimethyl acetal (1.2 mmol).
- 3.
Add Cu(OTf)2 (0.05–0.1 mmol).
- 4.
Monitor the reaction using TLC.
- 5.
When the reaction is completed, add Et3N (0.2 mmol) for quench Cu(OTf)2.
- 6.
Concentrate the mixture.
- 7.
Purify the reside using silica gel column chromatography (Note 2).
Notes
- 1.
In the case of mannoside, 2,3-O-benzylidene protected compound and 2,3- and 4,6-dibenzylidine protected compound are obtained when CSA and TsOH were used as catalysts. However, only 4,6-O-dibenzylidine protected compound was available when Cu(OTf)2 was employed as a catalyst.
- 2.
In the above protocol, purification was directly achieved using silica gel column chromatography without aqueous work-up. However, typical aqueous work-up can be used. When the benzylidene protected pyranosides are precipitated in the reaction mixture, the solid can be filtered through a glass filter and washed with appropriate solvent and water.
References
- 1.
- Wuts PGM. Greene’s protecting groups in organic synthesis. 5th ed. New Jersey: Wiley; 2014. 414-28 p. ISBN: 9781118057483. doi: 10.1002/9781118905074. [CrossRef]
- 2.
- Tran A-T, Jones RA, Pastor J, Boisson J, Smith N, Galan MC. Copper(II) triflate: A versatile catalyst for the one-pot preparation of orthogonally protected glycosides. Adv Synth Catal. 2011 Oct 10;353(14-15):2593–8. doi.org. [CrossRef]
Footnotes
The authors declare no competing or financial interests.
- Benzylidene protection of diol - Glycoscience Protocols (GlycoPODv2)Benzylidene protection of diol - Glycoscience Protocols (GlycoPODv2)
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