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With sodium hydroxide; In water; at 20 - 80℃; for 1h;pH 8 - 9; |
3.08 g (5.02 mmol) of chitotriitol trichloride was measured in a 200 mL eggplant flask, 2.24 g (21.10 mmol) of sodium carbonate was added, and 50 mL of methanol and 36 mL of water were added and the mixture was stirred. 1.4 mL (6.09 mmol) of dibutyl dicarbonate was added, then, after stirring for 14 hours the solvent of the reaction mixture solution was evaporated. 58 mL of methanol was added to the residual substance and was stirred, and 1.45 mL (11.92 mmol) of p-methoxybenzaldehyde was added, and the mixture was stirred for 24 hours. The solvent of the reaction mixture solution was evaporated, 43 mL of pyridine was added to the residual substance, and it was stirred in a water bath, and 11.3 mL (11.98 mmol) of acetic anhydride was added, and it was stirred for 17 hours. 21 mL of methanol was added on an ice bath and agitation was continued for 15 more minutes. The solvent of the reaction mixture solution was evaporated, and extracted (150 mL of chloroform /100 mL of water ×2) organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated. 20 mL of dimethylformamide was added to the residue, and after the residue was dissolved, the solvent was evaporated and the residual substance (about 7.2 g) was obtained. 25 mL of ethyl acetate was added to the residual substance, 25 mL of 1 mol/L hydrochloric acid was added under agitation at room temperature, and agitation was continued for 1 hour. The reaction liquid was washed with ethyl acetate (25 mL×4), a basic aqueous solution (15 mL of 5% sodium acetate aqueous solution + 35 mL of saturated sodium carbonate aqueous solution) was added, and adjusted to pH 8 and extracted (chloroform 50 mL×2). The organic layer was washed with 100 mL of saturated sodium bicarbonate, dried over anhydrous sodium sulfate, and the solvent was evaporated to obtain 3.09 g (3.14 mmol, yield: 62.7%, pale yellow crystal) of "Compound 5." 5.62 g (9.45 mmol) of 3,3- bis(dibenzylphosphoryl)propanoic acid and 853 mg (6.31 mmol) of HOBt·H2O were added to 3.09 g (3.14 mmol) of "Compound 5," and dissolved in 70 mL of dimethylformamide. 1.65 mL (9.39 mmol) of WSCD was added in an ice bath under agitation, and the resulting mixture was stirred for 17 hours. The solvent of the reaction mixture solution was evaporated and extracted (chloroform 150 mL/saturated sodium bicarbonate aqueous solution 100 mL, water 100 mL + saturated sodium chloride aqueous solution 20 mL×3, saturated sodium chloride aqueous solution 100 mL), and the organic layer was dried over anhydrous sodium sulfate and the solvent was evaporated and the residual substance (about 7.4 g, pale yellow crystal) was obtained. The residual substance was subjected to column chromatography (Silica gel N60 (trade name, manufactured by Kanto Chemical Co., Inc.) 250 g, chloroform/methanol = 20/1), and the crude product (Fr 2-3; 1.30 (yellow oily substance) and Fr 4-6; 842 mg (pale yellow crystal)) were obtained from Fractions 2 to 3 (about 600 to 900 mL; 300 mL) and Fractions 4 to 6 (about 900 to 1200 mL; 300 mL). After the crude product of Fraction 2 to 3 was subjected to column chromatography (Silica gel N60 (trade name, manufactured by Kanto Chemical Co., Inc.) 100 g, hexane/ethyl acetate/methanol =12/8/1) to elute high polarity impurities by 1000 mL of mobile phase and then the object fraction was eluted by chloroform/methanol = 10/1, and 831 mg (pale yellow crystal) of "Compound 6" was obtained. In the meantime, the crude product of Fractions 4 to 6 was subjected to column chromatography (Silica gel N60 (trade name, Manufactured by Kanto Chemical Co., Inc.) 100 g, ethyl acetate/chloroform/methanol =10/5/1) and 286 mg (pale yellow crystal) of "Compound 6" was obtained from fractions 11 to 13 (ca. 280 to 340 mL). 1.12 g (0.523 mmol, yield: 16.6%) of "Compound 6" was obtained from this reaction in total. The following numbers were assigned to carbon atoms in the analysis by 1H-nmr of "Compound 6." [] 1H-nmr (500MHz, CDCl3, delta) : 4.42(1H, m, 1), 3.92(1H, m, 1), 4.32(1H, m, 2), 5.05(1H, m, 3), 3.94(1H, m, 4), 5.29(1H, m, 5), 4.49(1H, dd, J=12, 2Hz, 6), 4. 12(1H, dd, J=12, 6Hz, 6), 4.92(1H, d, J=10Hz, 2-NH) , 4.81(1H, br. d, H=7Hz, 1'), 3.94(1H, m, 2'), 5.09(1H, t, J=10Hz, 3'), 3.63(1H, t, J=10Hz, 4'), 3.46(1H, m, 5'), 4.31(1H, m, 6'), 4.25(1H, m, 6'), 4.53(1H, d, J=8Hz, 1"), 3.88(1H, m, 2") , 5.16(1H, t, J=10Hz, 3"), 5. 02 (1H, m, 4"), 3. 60 (1H, m, 5"), 4. 36 (1H, dd, J=13, 4Hz, 6"), 3. 99 (1H, dd, J=13, 2Hz, 6") , 6. 57 (1H, d, J=9Hz, 2"-NH) , 2. 08 (3H, s, 6'-Ac), 2. 05 (3H, s, 6"-Ac), 2. 03 (3H, s, 1-Ac), 1. 982 (3H, s, 4"-Ac), 1. 977 (3H, s, 6-Ac), 1. 96 (3H, s, 3-Ac), 1. 95 (3H, s, 5'-Ac), 1. 85 (3H, s, 3'-Ac), 1. 81 (3H, s, 3"-Ac), 1. 41 (9H, s, - C (CH3)3), 2. 68~2. 89 ((2H, m, -COCH2CH-), 3. 28~3. 46 (1H, m, -COCH2CH-), 7. 24~7. 32 (20H, -CH2-Ar), 4. 92~5. 05 (8H, -CH2-Ar)13C-nmr (500MHz, CDCl3, delta) : 63. 18, 49. 02, 69. 44, 74. 01. 69. 29, 62. 30, 99. 14, 54. 86, 72. 52, 75. 95, 72.80, 62. 10, 100. 95, 54. ... |
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