Reacción #9810

Ecuación de reacción

Uridine 5′-triphosphate

tributylammonium

Uridine 5′-monophosphate

Carbonyldiimidazole

→

diuridine tetraphosphate

Disolventes

DMF

tributylamine

tributylamine

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroThe solution was evaporated in vacuo at 40° C. to an oil
2. 2
   workup.DISSOLUTIONThe residue was dissolved in dry DMF (Aldrich, 8 mL)
3. 3
   Otroto form a solution
4. 4
   workup.ADDITIONwas added to the reaction solution
5. 5
   Otrowas evaporated in vacuo to an oil
6. 6
   workup.DISSOLUTIONredissolved in water (5 mL)
7. 7
   Otropurified by column (300×50 mm) chromatography (Sephadex DEAE-A25, 40–120μ, Aldrich
8. 8
   Lavadopre-swollen in 1.0 M NaHCO3 and washed with 2 column volumes of deionized H2O (H2O→0.30 M NH4HCO3 gradient)
9. 9
   ConcentraciónThe pure fractions were concentrated in vacuo at 35° C.
10. 10
    workup.ADDITIONH2O added
11. 11
    Otroreevaporated 5 times

Procedimiento

Uridine 5′-monophosphate (Sigma, Milwaukee, 3.0 g, 9.26 mmol) was dissolved in dry DMF (10 mL) and tributylamine (Aldrich, 2 mL). The solution was evaporated in vacuo at 40° C. to an oil. The residue was dissolved in dry DMF (Aldrich, 8 mL) to form a solution. Carbonyldiimidazole (Aldrich, 1.65 g, 10.18 mmol) was added to this solution. The reaction was heated at 50° C. for one hour. Uridine 5′-triphosphate (Yamasa, 5.60 g, 10.18 mmol) prepared as the anhydrous tributylammonium salt in DMF (5 mL) and tributylamine (2 mL), as described in Example 3 below, was added to the reaction solution. The mixture was allowed to stir at 50° C. for three days when the solution was evaporated in vacuo to an oil, redissolved in water (5 mL) and purified by column (300×50 mm) chromatography (Sephadex DEAE-A25, 40–120μ, Aldrich, pre-swollen in 1.0 M NaHCO3 and washed with 2 column volumes of deionized H2O (H2O→0.30 M NH4HCO3 gradient). The pure fractions were concentrated in vacuo at 35° C., and H2O added and reevaporated 5 times to obtain diuridine tetraphosphate tetrammonium salt as a white solid (2.37 g, 30% yield): 92.11% pure by HPLC with the same retention time as the standard. In addition, the tetrammonium salt was analyzed by FABMS to give a mass of [C18H25N4O23P4 (M-H+)−: calculated 788.9860] 788.9857, confirming a parent formula of C18H26N4O23P4 for the free acid].

Fuente