(1S,5R)-6,8-dioxabicyclo[3.2.1]oct-2-en-4-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Levoglucosenone, an isomer of HMF, can be produced from woody (lignocellulosic) material through pyrolysis. F. Shafizadeh et al. (Carbohydrate Research, 71, (1979), 169-191) found that heating levoglucosenone in 0.5 M HCl (pH=0.3) in a boiling water bath to reaction completion (2.5 hours) produced HMF in a 16% yield. Heating levoglucosenone in 2 M acetic acid (pH=2.2) produced 1,6-anhydro-3-deoxy-β-D-erythro-hexopyranos-2-ulose, (represented by Formula (I-a)) in a 77% yield, but no HMF. to reaction completion (2.5 hours) produced HMF in a 16% yield

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1,6-anhydro-4-O-benzyl-3-deoxy-β-D-erythro-hexopyranos-2-ulose in benzyl alcohol was prepared as described in Example 6, except that 0.088 g of levoglucosenone were used as starting material and, 5 min after the addition of potassium benzoxide, a suspension of sodium borohydride (0.073 g) in ethanol (4 ml) was added to the mixture, which was then stirred for 0.5 h at room temperature, made neutral with acetic acid, evaporated under vacuum, and the resulting white residue transferred to a short column of silica, which was eluted with a gradient of ethyl acetate/hexane (from 1:2 to 2:1). The fractions found by t.l.c. to contain the title compound A were combined and evaporated, to give material that spontaneously crystallized (0.106 g, 64% from levoglucosenone). 1H-Nmr spectroscopy of this material showed it to be an 9:11 mixture of the title compound A and the D-arabino isomer determined from the relative intensities of their H-3 resonances. material and, 5 min was added to the mixture, which evaporated under vacuum was eluted with a gradient of ethyl acetate/hexane (from 1:2 to 2:1) evaporated to give material that spontaneously crystallized (0.106 g, 64% from levoglucosenone) an 9:11 mixture of the title compound A

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Levoglucosenone, an isomer of HMF, can be produced from woody (lignocellulosic) material through pyrolysis. F. Shafizadeh et al. (Carbohydrate Research, 71, (1979), 169-191) found that heating levoglucosenone in 0.5 M HCl (pH=0.3) in a boiling water bath to reaction completion (2.5 hours) produced HMF in a 16% yield. Heating levoglucosenone in 2 M acetic acid (pH=2.2) produced 1,6-anhydro-3-deoxy-β-D-erythro-hexopyranos-2-ulose, (represented by Formula (I-a)) in a 77% yield, but no HMF. to reaction completion (2.5 hours) produced HMF in a 16% yield

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Levoglucosenone, an isomer of HMF, can be produced from woody (lignocellulosic) material through pyrolysis. F. Shafizadeh et al. (Carbohydrate Research, 71, (1979), 169-191) found that heating levoglucosenone in 0.5 M HCl (pH=0.3) in a boiling water bath to reaction completion (2.5 hours) produced HMF in a 16% yield. Heating levoglucosenone in 2 M acetic acid (pH=2.2) produced 1,6-anhydro-3-deoxy-β-D-erythro-hexopyranos-2-ulose, (represented by Formula (I-a)) in a 77% yield, but no HMF. to reaction completion (2.5 hours) produced HMF in a 16% yield

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [D] 19 g of 1,6-anhydro-3,4-dideoxy-β-D-galactopyranose (7) prepared in the step [C] was dissolved in 100 ml of dichloromethane, forming a solution. Then, 50 g of active manganese dioxide was added to this solution, and the solution was stirred for 2 at room temperature, thus causing a reaction. Upon completion of the reaction, manganese dioxide was filtered off, and the solvent was distilled off under reduced pressure, whereby 15.3 g of levoglucosenone (8) (i.e., 1,6-anhydro-3,4-dideoxy-β-D-glycero-hex-3-enopyranos-2-ulose) was obtained at a yield of 82%. This substance exhibited the following physical properties: forming a solution a reaction was filtered off the solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: [D] 19 g of 1,6-anhydro-3,4-dideoxy-β-D-galactopyranose (7) prepared in the step [C] was dissolved in 100 ml of dichloromethane, forming a solution. Then, 50 g of active manganese dioxide was added to this solution, and the solution was stirred for 2 at room temperature, thus causing a reaction. Upon completion of the reaction, manganese dioxide was filtered off, and the solvent was distilled off under reduced pressure, whereby 15.3 g of levoglucosenone (8) (i.e., 1,6-anhydro-3,4-dideoxy-β-D-glycero-hex-3-enopyranos-2-ulose) was obtained at a yield of 82%. This substance exhibited the following physical properties: forming a solution a reaction was filtered off the solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Thereafter, one part by weight of the 2-hydroxy dideoxy derivative (7) is dissolved in 10 to 50 parts by weight, preferably 20 parts by weight, of an organic solvent, preferably dichloromethane, thus forming a solution. 3 to 20 parts by weight of an oxidizing reagent, preferably 5 parts by weight thereof, is added to the solution thus prepared, thereby forming a mixture. This mixture is stirred at room temperature for 1 to 5 hours, thus causing a reaction in the mixture. Then, the oxidizing reagent is filtered off, and the solvent is distilled off under reduced pressure, whereby levoglucosenone (8) is obtained. thus forming a solution 3 to 20 parts by weight of an oxidizing reagent, preferably 5 parts by weight thereof, is added to the solution thus prepared forming a mixture a reaction in the mixture Then, the oxidizing reagent is filtered off the solvent is distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2.4 ml (1.5 mol) of methyl lithium was gradually added to 30 ml of a dry tetrahydrofuran solution containing 0.3 g of 1,6-anhydro-3,4-dideoxy-β-D-glycero-hex-3-enopyranos-2-ulose under starting at 0° C. under an inert atmosphere of nitrogen gas. Completion of the reaction was confirmed by thin layer chromatography, and then 0.25 ml of acetyl chloride was added to the reaction mixture. The ice bath was removed, and the reaction solution was returned to room temperature and further stirred for one hour. The solvent was distilled off under reduced pressure. To the residue, 200 ml of ethyl acetate was added. The mixture was washed three times with 200 ml of a saturated sodium chloride aqueous solution. Then, the organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (ethyl acetate: hexane=1:5) to obtain 0.29 g of the desired product (Compound No. 32). The NMR analytical data of this product are as follows. under starting at 0° C. under an inert atmosphere of nitrogen gas The ice bath was removed was returned to room temperature The solvent was distilled off under reduced pressure To the residue, 200 ml of ethyl acetate was added The mixture was washed three times with 200 ml of a saturated sodium chloride aqueous solution Then, the organic layer was dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure the obtained crude product was purified by silica gel column chromatography (ethyl acetate: hexane=1:5)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 9.5 ml (1 mol) of vinyl magnesium bromide was gradually added to 50 ml of a dry tetrahydrofuran solution containing 1 g of 1,6-anhydro-3,4-dideoxy-β-D-glycero-hex-3-enopyranos-2-ulose under stirring at 0° C. under an inert atmosphere of nitrogen gas. 30 minutes later, the ice bath was removed, and stirring was further continued for 30 minutes at room temperature. Completion of the reaction was confirmed by thin layer chromatography, and then a small amount of water was added to inactivate any excess Grignard reagent. Then, the solvent was distilled off under reduced pressure. The obtained crude product was dissolved in 200 ml of ethyl acetate and washed three times with 200 ml of a saturated sodium chloride aqueous solution. The organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the obtained syrup product was purified by silica gel column chromatography (ethyl acetate: hexane=1:2) to obtain 0.9 g of the desired product (Compound No. 27). The NMR analytical data of this product are as follows. 30 minutes later, the ice bath was removed stirring a small amount of water was added Then, the solvent was distilled off under reduced pressure The obtained crude product washed three times with 200 ml of a saturated sodium chloride aqueous solution The organic layer was dried over anhydrous sodium sulfate The solvent was distilled off under reduced pressure the obtained syrup product was purified by silica gel column chromatography (ethyl acetate: hexane=1:2)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 50 ml of a dry diethyl ether solution containing 20 g of 1,6-anhydro-3,4-dideoxy-β-D-glycero-hex-3-enopyranos-2-ulose, was gradually dropwise added to 500 ml of a dry diethyl ether suspension containing 3.0 g of lithium aluminum hydride, at 0° C. under an inert atmosphere of nitrogen gas. After completion of the dropwise addition, the mixture was immediately returned to room temperature, and stirring was continued for 30 minutes. Disappearance of the starting material was confirmed by thin layer chromatography, and then a small amount of water was added to inactivate an excess amount of lithium aluminum hydride. The mixture was further stirred for 30 minutes, and the reaction mixture was filtered through Celite® to remove the precipitate. The precipitate was washed a few times with diethyl ether, and the washing solutions were concentrated under reduced pressure together with the filtrate. Precipitated crude crystals were recrystallized from diethyl ether to obtain 14.5 g of the desired product (Compound No. 1). The NMR analytical data and physical properties of this product were as follows. at 0° C. After completion of the dropwise addition was immediately returned to room temperature The mixture was further stirred for 30 minutes the reaction mixture was filtered through Celite® to remove the precipitate The precipitate was washed a few times with diethyl ether the washing solutions were concentrated under reduced pressure together with the filtrate Precipitated crude crystals were recrystallized from diethyl ether

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 100 mg of 1,6-anhydro-3,4-dideoxy-β-D-glycero-hex-3-enopyranos-2-ulose was dissolved in 3 ml of propionic anhydride, and the solution was cooled to -20° C. Then, 0.06 ml of concentrated sulfuric acid was added thereto, and the mixture was stirred for 30 minutes. Then, the reaction mixture was added to 100 ml of an ice-cooled saturated sodium hydrogencarbonate aqueous solution. The mixture was stirred for 30 minutes and then extracted with 100 ml of ethyl acetate. The extract was washed three times with 100 ml of a saturated sodium chloride aqueous solution. The organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained syrup crude product was purified by silica gel column chromatography (ethyl acetate: hexane=1:2) to obtain 100 mg of the desired product (Intermediate No. 19) as a colorless transparent liquid. The NMR analytical data of this product are as follows. The mixture was stirred for 30 minutes extracted with 100 ml of ethyl acetate The extract was washed three times with 100 ml of a saturated sodium chloride aqueous solution The organic layer was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The obtained syrup crude product was purified by silica gel column chromatography (ethyl acetate: hexane=1:2)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 150 ml of a dry pyridine-carbon tetrachloride (1:1) solution containing 40 g of iodine, was gradually added at 0° C. to 150 ml of a dry pyridine-carbon tetrachloride (1:1) solution containing 5 g of 1,6-anhydro-3,4-dideoxy-β-D-glycero-hex-3-enopyranos-2-ulose (disclosed in U.S. Pat. No. 3,926,947) under an inert atmosphere of nitrogen gas. The mixture was stirred at room temperature for two hours. Then, disappearance of the starting material was confirmed by thin layer chromatography, and 200 ml of ethyl acetate was added thereto. The mixture was washed twice with 200 ml of a saturated sodium chloride aqueous solution and once with 200 ml of 20% sodium thiosulfate. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained syrup crude product was purified by silica gel column chromatography (ethyl acetate: hexane=1:3) to obtain 6.1 g of the desired product (Intermediate No. 5) as slightly yellow crystals. The NMR analytical data and physical data of this product are as follows. was added The mixture was washed twice with 200 ml of a saturated sodium chloride aqueous solution and once with 200 ml of 20% sodium thiosulfate The organic layer was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The obtained syrup crude product was purified by silica gel column chromatography (ethyl acetate: hexane=1:3)