Ribofuranosyl purine compounds, methods for preparing the same and use thereof
a technology of ribofuranosyl and purine, which is applied in the field of ribofuranosyl purine compounds, can solve the problems of bad oral availability of said compounds, and achieve the effects of less reaction steps, improved yield and simple operation
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example 1
Preparation of 2-amino-6-hydroxyl-9-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl)purine (2)
[0066]
[0067]At room temperature, dried guanosine 1 (11.3 g, 40 mmol), triethylamine (22.9 mL, 158.4 mmol) and acetic anhydride (13.6 mL, 144 mmol) were respectively dissolved in 500 ml anhydrous acetonitrile, and 4-dimethylamino pyridine (366 mg, 3 mmol) was added therein. The resultant mixed solution was sharply stirred at room temperature for 30 min, and then continuously stirred for 10 min after 5 ml anhydrous methanol was added. The solvent was evaporated under reduced pressure, and the resultant solid was recrystallized with 180 mL isopropanol to obtain white crystals 2 (15.7 g, 96%), m.p 229-231° C.; 1H NMR (300 MHz, DMSO-d6) δ 10.75 (1H, br s), 7.94 (1H, s), 6.55 (2H, br s), 5.98 (1H, d, J=4.8 Hz), 5.79 (1H, t, J=5.5 Hz), 5.59 (1H, t, J=5.5 Hz), 4.40-4.24 (3H, m), 2.11 (3H, s), 2.04 (3H, s), 2.03 (3H, s).
example 2
Preparation of 2-amino-6-chloro-9-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl) purine (3)
[0068]
[0069]Anhydrous acetonitrile (15 mL) and anhydrous 1,2-dichloroethane (30 mL) were placed into a 100 ml three-necked bottle. While stirring at room temperature, 10.0 g (24.4 mmol) compound 2, 11.0 g (66.4 mmol) Et4NCl and 16.8 g (10.0 mL, 109.6 mmol) POCl3, and 4.78 g (5.0 mL, 35.1 mmol) N,N-dimethylaniline were successively added therein, and rapidly heated to reflux. After holding 20-25 min, the resultant mixed solution was slowly and dropwise added to brash ice and stirred, and 10 mL 1,2-dichloroethane was supplemented. After brash ice was completely dissolved, the resultant mixed solution was poured into a 250 mL separating funnel for separation. After the aqueous phase was extracted three times with 50 mL 1,2-dichloroethane, the organic phases were combined together and adjusted to a pH of 7 with cold 5% sodium carbonate solution, then a liquid separation was carried out. The organic pha...
example 3
Preparation of 2-methylthio-6-chloro-9-(2′,3′,5′-tri-O-acetyl-β-D-ribofuranosyl) purine (4a)
[0071]Compound 3 (2.5 g, 5.85 mmol) and dimethyl disulfide (29.25 mmol) were respectively added to 35 mL anhydrous acetonitrile, then nitrogen gas was fed to the mixed solution, and at room temperature, the mixed solution was stirred for 30 min, and then isoamyl nitrite (4.25 g, 36.3 mmol) was immediately added to the mixed solution. The resultant mixed solution was continuously stirred at room temperature for 10 min, and then transferred to an oil bath at 60° C., and heated for 4-8 hours. After it was detected with TLC (EtOAc-P.E., 1:1) that the starting materials disappeared, the solvent was evaporated under reduced pressure, and the residue was isolated by column chromatography (silica gel, EtOAc-P.E., 2:3, 1:1) to obtain a light yellow oily liquid 4a, with a yield of 66%; 1H NMR (300 MHz, CDCl3): δ 8.09 (1H, s), 6.09 (1H, d, J=4.5 Hz), 5.97 (1H, t, J 5.4 Hz), 5.62 (1H, t, J=5.4 Hz), 4.45-...
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