[Synthesis]
The general procedure for the synthesis of 1-((2R,3R,4R,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)-4-hydroxy-3-methoxytetrahydrofuran-2-yl)pyrimidine-2,4(1H,3H)-diones from magnesium methanolate and N/A is as follows: following the literature methodology, a two-step reaction was carried out to prepare 5'-O-DMT-2,2'-O -anhydrouridine (6). Subsequently, compound 6 was converted to 5'-O-DMT-2'-O-methyluridine with reference to the method reported in the literature. This was done as follows: first, magnesium powder (0.5 g) was heated in methanol (50 mL) at 60 °C for 2 h. Excess methanol was evaporated and dried under vacuum to obtain magnesium methanolate in gray powder form. The dried magnesium methanolate (740 mg, 8.57 mmol, 6.00 eq.) was added to a suspension of compound 6 (750 mg, 1.42 mmol, 1.00 eq.) in DMF (20 mL), and the mixture was heated to 100 °C for 2 h. The reaction was carried out until the solution was clarified. After completion of the reaction, the solvent was removed by evaporation and the residue was dissolved in ethyl acetate. The organic layer was washed sequentially with NaHCO3 solution and water, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with the eluent being a dichloromethane solution containing 2-4% methanol to give compound 7 (510 mg, 0.91 mmol, 64% yield) as a white solid.1H NMR (400 MHz, CDCl3): δ (ppm) = 3.54-3.57 (m, 2H, H-C(5')), 3.65 (s, 3H, 2' -OCH3), 3.79-3.80 (m, 7H, H-C(2'), DMT-OCH3), 3.98-4.01 (m, 1H, H-C(4')), 4.45-4.50 (m, 1H, H-C(3')), 5.26 (d, 1H, J = 8.1 Hz, H-C(5)), 5.97 (s, 1H, H-C(1' )), 6.82-6.86 (m, 4H, DMT-Har), 7.24-7.39 (m, 9H, DMT-Har), 8.03 (d, 1H, J = 8.1 Hz, H-C(6)); MS (ESI): m/z = 583.1 [M + Na]+. |