3-O-Benzyl-1,2,5,6-di-O-isopropylidene-alpha-D-glucofuranose: Preparation and Applications in Chemical Biology

General Description

3-O-Benzyl-1,2,5,6-di-O-isopropylidene-alpha-D-glucofuranose (3-O-B-DIP-alpha-D-Glu) is a sugar derivative of glucose with a benzyl group attached to the 3-position of the sugar ring. It is a synthetic sugar molecule that has been studied extensively in recent years due to its potential applications in medicinal chemistry, biochemistry, and drug delivery. 3-O-Benzyl-1,2,5,6-di-O-isopropylidene-alpha-D-glucofuranose is an important intermediate in the synthesis of a variety of compounds and has been used in numerous pharmaceutical formulations.

Figure 1. Properties of 3-O-Benzyl-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose

Preparation

Figure 2. Synthesis of 3-O-Benzyl-1,2,5,6-di-O-isopropylidene-alpha-D-glucofuranose

Dissolve D-glucose (15 g, 57.69 mmol) in DMF (144 mL). Add Benzyl bromide (10.09 mL, 86.53 mmol) to the reaction mixture and stir for 5 min. Cool the reaction mixture to 0°C. Add NaH (3.75 g, 95.18 mmol) in portions (1.25 gx3) to the cooled solution (0°C) and stir the reaction mixture for 2 hours at room temperature (24°C). Quench the reaction with IPA (6 mL) at 0°C followed by the slow addition of H₂O (115 mL) at 0°C. Extract the resulting mixture with EtOAc (100 mLx3). Concentrate the organic phase under reduced pressure, dry over MgSO4, filter and purify by flash column chromatography (EtOAc-hexane, 1 : 3 to 1 : 1).¹

Applications

Intermediate in Synthesis of 1,3 β-glucan hexasaccharide

Figure 3. Intermediate in Synthesis of 1,3 β-glucan hexasaccharide

Add a solution of 6 M HCl (25 mL) to a solution of 3-O-Benzyl-1,2,5,6-di-O-isopropylidene-alpha-D-glucofuranose (50 g, 0.143 mol) in dioxane (100 mL). Stir the mixture overnight at room temperature. Add dichloromethane (DCM) (50 mL) to the reaction mixture. Separate the yellowish organic layer and discard. Neutralize the aqueous layer by adding a solution of satd Na₂CO₃. Extract the mixture with EtOAc (375 mL). Remove the organic solvent under reduced pressure. Obtain a white pasty material. Dissolve the white pasty material in a small amount of EtOAc. Keep the mixture in fridge. Crystallize 3-O-benzyl-α/β-D-glucopyranose.²

Intermediate in Synthesis of(-)-Jaspine B

Figure 4. Intermediate in Synthesis of(-)-Jaspine B

Stir the solution of reactant (2.0 g, 5.7 mmol) and periodic acid (1.55 g, 6.8 mol) in 80 mL of dry ethyl acetate for 2 h. Separate the solid by filtration. Evaporate under reduced pressure to obtain a colorless syrup. Dissolve the syrup in 50 mL of THF. Add the solution dropwise to the solution of phosphorus ylide previously prepared [tridecyltriphenylphosphonium bromide (3.6 g, 6.84 mmol) in 150 mL of dry THF under an atmosphere of argon. Cool the mixture at 0 °C and add n-butyllithium dropwise (5.13 mL, 8.2 mmolof THF solution 1.6 M). Stir the reaction mixture for 30 min]. Stir the resulting reaction mixture for 4 h 0 °C. Stop the reaction by adding 50 mL of water. Extract the reaction with ethyl acetate (3 Χ50 mL). Dry the combined organic phase over Na₂SO₄. Concentrate the reaction mixture under reduced pressure. Purify the residue by column chromatography to obtain the product.³

Intermediate in Synthesis of D-xylofuranose-derived t-butanesulfinyl aldimines

Figure 5. Intermediate in Synthesis of D-xylofuranose-derived t-butanesulfinyl aldimines

Prepare a solution of O-benzyl-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose (3.16 g, 9.0 mmol) in THF (11 mL). Add 2 M aq. HCl (11 mL) at r.t., Continue stiring for 5 h. Quench the reaction by adding NaHCO₃(1.8 g). Stir the mixture for 15 min and extract with EtOAc (3 × 40 mL). Dry the combined organic layer (Na₂SO₄). Filter and concentrate under reduced pressure to obtain a pale yellow oil (2.98 g). Dissolve the crude diol in CH₂Cl₂(5 mL) and add sat. aq. NaHCO₃(1.3 mL) and NaIO₄(3.85 g, 18.0 mmol). Continue stiring for 4 h and dilute the mixture with CH₂Cl₂(20 mL), dry(Na₂SO₄), filter and concentrate under reduced pressure to obtain a pale yellow oil (2.24 g). Prepare a solution of the crude aldehyde (1.25 g, 4.5 mmol) in CH₂Cl₂(5 mL) and add CuSO₄ (3.59 g, 22.5 mmol) and (SS)-t-BS-NH₂(653 mg, 5.4 mmol). Stir the mixture for 30 h, filter through Celite, concentrate under reduced pressure and purify by silica gel chromatography to obtain product(1.424 g, 70% over 3 steps).⁴

References

1. Sawant, Ratnnadeep C.; et al. RSC Advances (2015), 5(25), 19027-19033.

2. Elsaidi, Hassan R. H.; et al. Carbohydrate Research (2015), 408, 96-106.

3. Cruz-Gregorio, Silvano; et al. Tetrahedron Letters (2011), 52(48), 6370-637.

4. Wang, Bing; et al. Tetrahedron Letters (2012), 53(2), 119-122.