(3R,4R,5R,6R)-3-amino-6-(hydroxymethyl)oxane-2,4,5-triol;hydrochloride

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

Procedure: D-Galactosamine hydrochloride (hereinbelow abbreviated as D-galN, manufactured by Nakarai Tesque) and LPS were dissolved in water at final concentrations of 75 mg/ml and 0.1 or 0.2 μg/ml, respectively. Furthermore, the hydrochloride of Compound No. 33 in Test Example 1 was dissolved in a 5% dimethylsulfoxide-10% Nikkol (Nippon Surfactant Kogyo) solution at the final concentrations of 0, 0.25, 0.5 and 1 mg/ml, respectively.

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

Procedure: D-Galactosamine hydrochloride (hereinbelow abbreviated as D-galN, manufactured by Nakarai Tesque) and LPS were dissolved in water at final concentrations of 75 mg/ml and 0.1 or 0.2 μg/ml, respectively. Furthermore, the hydrochloride of Compound No. 33 in Test Example 1 was dissolved in a 5% dimethylsulfoxide-10% Nikkol (Nippon Surfactant Kogyo) solution at the final concentrations of 0, 0.25, 0.5 and 1 mg/ml, respectively.

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

Procedure: In 10 ml of DMF was dissolved 0.22 g of galactosamine hydrochloride (1.04×10-3 mol). After 0.15 ml (1.04×10-3 mol) of triethylamine was added to the solution, 0.30 g (1.84×10-3 mol, value calculated from apparent molecular weight per 1 unit) was added to the mixture. The reaction was carried out at room temperature for 2 days. Then the solution containing the precipitates was dialyzed (2 days) and then freeze dried to prepare a sample (charged amounts given herein are for the sample obtained by activation of the side chain using the polymer having a side chain hydrolysis rate of 28.6% described above. For other samples, about two-fold amounts of sugar and triethylamine were used in response to the rate of activation of the side chain). was added to the mixture Then the solution containing the precipitates was dialyzed (2 days) freeze dried to prepare a sample ( charged amounts obtained by activation of the side chain a side chain hydrolysis rate of 28.6%

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

Procedure: D-Galactosamine hydrochloride (hereinbelow abbreviated as D-galN, manufactured by Nakarai Tesque) and LPS were dissolved in water at final concentrations of 75 mg/ml and 0.1 or 0.2 μg/ml, respectively. Furthermore, the hydrochloride of Compound No. 33 in Test Example 1 was dissolved in a 5% dimethylsulfoxide-10% Nikkol (Nippon Surfactant Kogyo) solution at the final concentrations of 0, 0.25, 0.5 and 1 mg/ml, respectively.

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

Procedure: To a THF (20 ml) solution containing geranic acid (0.84 g, 5 mmols), triethylamine (0.51 g, 5 mmols) was added and cooled to 0° C., into which a THF (5 ml) solution containing isobutyl chloroformate (0.68 g, 5 mmols) was added dropwise, followed by 30 minutes' stirring at 0° C. Then galactosamine hydrochloride (1.08 g, 5 mmols) was dissolved in 10 ml of water, to which 5 ml of 1N sodium hydroxide was further added, and the solution was added to the reaction mixture all at a time. After the following stirring for an hour at 0° C. and for further 4 hours at room temperature, the reaction mixture was condensed under reduced pressure. To the residue 150 ml of acetone was added and precipitated sodium chloride was filtered off. The filtrate was condensed once again and the residue was separated on silica gel column chromatography. Consequently the product was obtained from the hexane-ethanol (2:1) distillate as a viscous oily substance, to which a minor amount of ether was added to crystallize the product. Through subsequent suction filtration, 0.754 g of the title compound was obtained. The yield was 46%, and the melting point was 85-87° C. was added was added dropwise was further added the solution was added to the reaction mixture all at a time After the following stirring for an hour at 0° C. and for further 4 hours at room temperature condensed under reduced pressure precipitated sodium chloride was filtered off condensed once again the residue was separated on silica gel column chromatography Consequently the product was obtained from the hexane-ethanol (2:1) distillate as a viscous oily substance, to which a minor amount of ether was added to crystallize the product Through subsequent suction filtration

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

Procedure: To a THF (20 ml) solution containing geranic acid (0.84 g, 5 mmols), triethylamine (0.51 g, 5 mmols) was added and cooled to 0° C., into which a THF (5 ml) solution containing isobutyl chloroformate (0.68 g, 5 mmols) was added dropwise, followed by 30 minutes' stirring at 0° C. Then galactosamine hydrochloride (1.08 g, 5 mmols) was dissolved in 10 ml of water, to which 5 ml of 1N sodium hydroxide was further added, and the solution was added to the reaction mixture all at a time. After the following stirring for an hour at 0° C. and for further 4 hours at room temperature, the reaction mixture was condensed under reduced pressure. To the residue 150 ml of acetone was added and precipitated sodium chloride was filtered off. The filtrate was condensed once again and the residue was separated on silica gel column chromatography. Consequently the product was obtained from the hexane-ethanol (2:1) distillate as a viscous oily substance, to which a minor amount of ether was added to crystallize the product. Through subsequent suction filtration, 0.754 g of the title compound was obtained. The yield was 46%, and the melting point was 85-87° C. was added was added dropwise was further added the solution was added to the reaction mixture all at a time After the following stirring for an hour at 0° C. and for further 4 hours at room temperature condensed under reduced pressure precipitated sodium chloride was filtered off condensed once again the residue was separated on silica gel column chromatography Consequently the product was obtained from the hexane-ethanol (2:1) distillate as a viscous oily substance, to which a minor amount of ether was added to crystallize the product Through subsequent suction filtration

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

Procedure: To a THF (20 ml) solution containing geranic acid (0.84 g, 5 mmols), triethylamine (0.51 g, 5 mmols) was added and cooled to 0° C., into which a THF (5 ml) solution containing isobutyl chloroformate (0.68 g, 5 mmols) was added dropwise, followed by 30 minutes' stirring at 0° C. Then galactosamine hydrochloride (1.08 g, 5 mmols) was dissolved in 10 ml of water, to which 5 ml of 1N sodium hydroxide was further added, and the solution was added to the reaction mixture all at a time. After the following stirring for an hour at 0° C. and for further 4 hours at room temperature, the reaction mixture was condensed under reduced pressure. To the residue 150 ml of acetone was added and precipitated sodium chloride was filtered off. The filtrate was condensed once again and the residue was separated on silica gel column chromatography. Consequently the product was obtained from the hexane-ethanol (2:1) distillate as a viscous oily substance, to which a minor amount of ether was added to crystallize the product. Through subsequent suction filtration, 0.754 g of the title compound was obtained. The yield was 46%, and the melting point was 85-87° C. was added was added dropwise was further added the solution was added to the reaction mixture all at a time After the following stirring for an hour at 0° C. and for further 4 hours at room temperature condensed under reduced pressure precipitated sodium chloride was filtered off condensed once again the residue was separated on silica gel column chromatography Consequently the product was obtained from the hexane-ethanol (2:1) distillate as a viscous oily substance, to which a minor amount of ether was added to crystallize the product Through subsequent suction filtration

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

Procedure: To a THF (20 ml) solution containing geranic acid (0.84 g, 5 mmols), triethylamine (0.51 g, 5 mmols) was added and cooled to 0° C., into which a THF (5 ml) solution containing isobutyl chloroformate (0.68 g, 5 mmols) was added dropwise, followed by 30 minutes' stirring at 0° C. Then galactosamine hydrochloride (1.08 g, 5 mmols) was dissolved in 10 ml of water, to which 5 ml of 1N sodium hydroxide was further added, and the solution was added to the reaction mixture all at a time. After the following stirring for an hour at 0° C. and for further 4 hours at room temperature, the reaction mixture was condensed under reduced pressure. To the residue 150 ml of acetone was added and precipitated sodium chloride was filtered off. The filtrate was condensed once again and the residue was separated on silica gel column chromatography. Consequently the product was obtained from the hexane-ethanol (2:1) distillate as a viscous oily substance, to which a minor amount of ether was added to crystallize the product. Through subsequent suction filtration, 0.754 g of the title compound was obtained. The yield was 46%, and the melting point was 85–87° C. was added was added dropwise was further added the solution was added to the reaction mixture all at a time After the following stirring for an hour at 0° C. and for further 4 hours at room temperature condensed under reduced pressure precipitated sodium chloride was filtered off condensed once again the residue was separated on silica gel column chromatography Consequently the product was obtained from the hexane-ethanol (2:1) distillate as a viscous oily substance, to which a minor amount of ether was added to crystallize the product Through subsequent suction filtration

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

Procedure: In 10 ml of DMF was dissolved 0.22 g of galactosamine hydrochloride (1.04×10-3 mol). After 0.15 ml (1.04×10-3 mol) of triethylamine was added to the solution, 0.30 g (1.84×10-3 mol, value calculated from apparent molecular weight per 1 unit) was added to the mixture. The reaction was carried out at room temperature for 2 days. Then the solution containing the precipitates was dialyzed (2 days) and then freeze dried to prepare a sample (charged amounts given herein are for the sample obtained by activation of the side chain using the polymer having a side chain hydrolysis rate of 28.6% described above. For other samples, about two-fold amounts of sugar and triethylamine were used in response to the rate of activation of the side chain). was added to the mixture Then the solution containing the precipitates was dialyzed (2 days) freeze dried to prepare a sample ( charged amounts obtained by activation of the side chain a side chain hydrolysis rate of 28.6%

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

Procedure: D-Galactosamine hydrochloride (hereinbelow abbreviated as D-galN, manufactured by Nakarai Tesque) and LPS were dissolved in water at final concentrations of 75 mg/ml and 0.1 or 0.2 μg/ml, respectively. Furthermore, the hydrochloride of Compound No. 33 in Test Example 1 was dissolved in a 5% dimethylsulfoxide-10% Nikkol (Nippon Surfactant Kogyo) solution at the final concentrations of 0, 0.25, 0.5 and 1 mg/ml, respectively.