[Synthesis]
GENERAL STEPS: To a solution of guanosine (1 g, 3.53 mmol) in pyridine (25 mL) was added trimethylsilyl chloride (TMSCl) (3.35 mL, 26.47 mmol). The reaction mixture was stirred at room temperature for 2 hours. Subsequently, the reaction system was cooled to 0°C and isobutyryl chloride was slowly added. After addition, the reaction solution was returned to room temperature and continued stirring. Upon completion of the reaction, water (10 mL) was slowly added at 0 °C, followed by additional water (10 mL) at 5 °C. After 5 min, ammonia (NH4OH) was added. after 15 min, water (50 mL) and dichloromethane (CH2Cl2) (20 mL) were added for extraction. The aqueous phase was separated and concentrated under reduced pressure, the resulting solid was recrystallized with hot water, filtered and the solvent was evaporated under reduced pressure to afford the target compound N-(9-(((2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)isobutyramide (82% yield). The product was confirmed by 1H-NMR (200 MHz, DMSO-d6), ESI MS characterization.1H-NMR (200 MHz, DMSO-d6) δ: 1.10,1.13 (6H, s, (CH3)2CH), 2.75-2.76 (1H, m, CH), 3.56-3.59 (2H, m, H-5'), 3.88- 3.90 (1H, m, H-4'), 4.11-4.13 (1H, m, H-3'), 4.41-4.44 (1H, m, H-2'), 5.04 (1H, t, J=4.6 Hz, OH-5'), 5.45 (1H, d, J=3.8 Hz, OH-3'), 5.48 (1H, d, J=4.0 Hz, OH-2 '), 5.80 (1H, d, J=5.4Hz, H-1'), 8.26 (1H, s, H-8), 11.90 (1H, br s, NH-CO), 12.16 (1H, br s, NH-3).ESI MS: m/z 354.2Da [M+H]+, molecular formula C14H19N5O6, molecular weight 353.33. |
[References]
[1] European Journal of Medicinal Chemistry, 2012, vol. 54, p. 202 - 209
[2] Bioorganic and medicinal chemistry, 2003, vol. 11, # 2, p. 235 - 249
[3] Patent: US2011/86813, 2011, A1. Location in patent: Page/Page column 30
[4] Nucleosides, Nucleotides and Nucleic Acids, 2004, vol. 23, # 1-2, p. 171 - 181
[5] Patent: EP1710249, 2006, A1. Location in patent: Page/Page column 17 |