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

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Example 3-Synthesis of Galβ1-3GlcNH2 βSEt and Galβ1-3GalNH2 βSEt. See example 1, similar conditions and enzyme may be used, but instead GlcNH2 βSEt, or GalNH2 βSEt to obtain the latter product, is used as the acceptor. Here, extraction is less favorable for isolation, and instead ion-exchanger as above may be used followed by e.g. precipitation or a second chromatographic step.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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%

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 250 ml round bottom flash, charged with 10.0 g (0.041 mole) of N ε-(tert-butoxy carbonyl) L-lysine 27, commercially available from BACHEM Bioscience Inc. (subsidiary of BACHEM Switzerland, 3700 Horizon Drive, Renaissance at Gulph Mills, King of Prussia, Pa., 19406, USA), and 100 ml of methanol is added 10.0 g (0.07 mole) of ethyl trifluoroacetate followed by 20.0 ml (0.144 mole) of triethylamine. The mixture is stirred at 20-300° C. for 20 hours and then concentrated via rotary evaporation. The residue is diluted with 50 ml of diethyl ether and then filtered. The filtrate is then washed with 3×30 ml aliquots of 1N aqueous HCL, 20 ml of deionized water, and finally with 20 ml of deionized water. The organic phase is dried over anhydrous magnesium sulfate, filtered and concentrated. The residue is distilled under vacuum to yield product 28 in good yield. N ε-(tert-butoxy carbonyl) N1-α-trifluoroacetyl L-lysine is reacted with tri-o-acetyl tet-Gal-NAC 1-a-S-Pentylamine in the presence of a BOP reagent. The activated carboxylic acid reacts with the clustered galactosamine in DBIF and Triethylamine to afford galactose cluster lyEsine adduct 29 in good yield. The N a-trifluoroacetyl protection of the lysine is removed to afford Primary α-amino lysine-galactose cluster 29a in moderate yield.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 4.60 g (10 mmol) of 5-methyl-(6R,S)-tetrahydrofolic acid were added portion-wise and completely dissolved in 30 ml of an aqueous solution of D-galactosamine (3.58 g, 20 mmol) stirred under nitrogen. The resulting solution (pH 6.53) was freeze-dried, obtaining 8.72 g of the title product. The resulting solution (pH 6.53) was freeze-dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Example 3-Synthesis of Galβ1-3GlcNH2 βSEt and Galβ1-3GalNH2 βSEt. See example 1, similar conditions and enzyme may be used, but instead GlcNH2 βSEt, or GalNH2 βSEt to obtain the latter product, is used as the acceptor. Here, extraction is less favorable for isolation, and instead ion-exchanger as above may be used followed by e.g. precipitation or a second chromatographic step.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Example 3-Synthesis of Galβ1-3GlcNH2 βSEt and Galβ1-3GalNH2 βSEt. See example 1, similar conditions and enzyme may be used, but instead GlcNH2 βSEt, or GalNH2 βSEt to obtain the latter product, is used as the acceptor. Here, extraction is less favorable for isolation, and instead ion-exchanger as above may be used followed by e.g. precipitation or a second chromatographic step.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 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.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 250 ml round bottom flash, charged with 10.0 g (0.041 mole) of N ε-(tert-butoxy carbonyl) L-lysine 27, commercially available from BACHEM Bioscience Inc. (subsidiary of BACHEM Switzerland, 3700 Horizon Drive, Renaissance at Gulph Mills, King of Prussia, Pa., 19406, USA), and 100 ml of methanol is added 10.0 g (0.07 mole) of ethyl trifluoroacetate followed by 20.0 ml (0.144 mole) of triethylamine. The mixture is stirred at 20-30° C. for 20 hours and then concentrated via rotary evaporation. The residue is diluted with 50 ml of diethyl ether and then filtered. The filtrate is then washed with 3×30 ml aliquots of 1N aqueous HCL, 20ml of deionized water, and finally with 20 ml of deionized water. The organic phase is dried over anhydrous magnesium sulfate, filtered and concentrated. The residue is distilled under vacuum to yield product 28 in good yield. N ε-(tert-butoxy carbonyl) N1α-trifluoroacetyl L-lysine is reacted with tri-o-acetyl tet-Gal-NAC 1-a-S-Pentylamine in the presence of a BOP reagent. The activated carboxylic acid reacts with the clustered galactosamine in DMF and Triethylamine to afford galactose cluster lysine adduct 29 in good yield. The N α-trifluoroacetyl protection of the lysine is removed to afford Primary α-amino lysine-galactose cluster 29a in moderate yield.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 250 ml round bottom flash, charged with 10.0 g (0.041 mole) of N ε-(tert-butoxy carbonyl) L-lysine 27, commercially available from BACHEM Bioscience Inc. (subsidiary of BACHEM Switzerland, 3700 Horizon Drive, Renaissance at Gulph Mills, King of Prussia, Pa., 19406, USA), and 100 ml of methanol is added 10.0 g (0.07 mole) of ethyl trifluoroacetate followed by 20.0 ml (0.144 mole) of triethylamine. The mixture is stirred at 20-30° C. for 20 hours and then concentrated via rotary evaporation. The residue is diluted with 50 ml of diethyl ether and then filtered. The filtrate is then washed with 3×30 ml aliquots of 1N aqueous HCL, 20ml of deionized water, and finally with 20 ml of deionized water. The organic phase is dried over anhydrous magnesium sulfate, filtered and concentrated. The residue is distilled under vacuum to yield product 28 in good yield. N ε-(tert-butoxy carbonyl) N1α-trifluoroacetyl L-lysine is reacted with tri-o-acetyl tet-Gal-NAC 1-a-S-Pentylamine in the presence of a BOP reagent. The activated carboxylic acid reacts with the clustered galactosamine in DMF and Triethylamine to afford galactose cluster lysine adduct 29 in good yield. The N α-trifluoroacetyl protection of the lysine is removed to afford Primary α-amino lysine-galactose cluster 29a in moderate yield.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a 250 ml round bottom flash, charged with 10.0 g (0.041 mole) of N ε-(tert-butoxy carbonyl) L-lysine 27, commercially available from BACHEM Bioscience Inc. (subsidiary of BACHEM Switzerland, 3700 Horizon Drive, Renaissance at Gulph Mills, King of Prussia, Pa., 19406, U.S.A.), and 100 ml of methanol is added 10.0 g (0.07 mole) of ethyl trifluoroacetate followed by 20.0 ml (0.144 mole) of triethylamine. The mixture is stirred at 20-30°0 C. for 20 hours and then concentrated via rotary evaporation. The residue is diluted with 50 ml of diethyl ether and then filtered. The filtrate is then washed with 3×30 ml aliquots of 1N aqueous HCL, 20 ml of deionized water, and finally with 20 ml of deionized water. The organic phase is dried over anhydrous magnesium sulfate, filtered and concentrated. The residue is distilled under vacuum to yield product 28 in good yield. N ε-(tert-butoxy carbonyl) N1 -α-trifluoroacetyl L-lysine is reacted with tri-o-acetyl tet-Gal-NAC 1-a-S-Pentylamine in the presence of a BOP reagent. The activated carboxylic acid reacts with the clustered galactosamine in DMF and Triethylamine to afford galactose cluster lysine adduct 29 in good yield. The N α-trifluoroacetyl protection of the lysine is removed to afford Primary α-amino lysine-galactose cluster 29a in moderate yield.