Ammonia → Fludarabine

関与物質

反応手順

9-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)-2-fluoroadenine (II, 1.7 g, 3 mmol) was suspended in liquid NH3 (75 ml) with stirring and Na (410 mg, 18 g-atoms) was added in small portions. When a purple color persisted for a few minutes after the addition of Na, the mixture was neutralized with NH4Cl (920 mg, 18 mmol). The NH3 was evaporated in a stream of dry N2, and the residue was triturated with Et2O (75 ml). The insoluble solid that formed was collected by filtration and washed with H2O (three 3-ml portions) before it was recrystallized from H2O (65 ml) giving the crude produce (479 mg), which was shown by TLC (4:1 CHCl3 -MeOH) to be primarily a mixture of I and 9-β-D-arabinosyladenine. A solution of the crude product in H2O (1 ml/mg) was percolated through an ion-exchange column [10 g of Amberlite (CG50, 100-200 Mexh)/mmol of nucleoside] at a rate not exceeding 0.5 ml/min, and the column was eluted with H2O until elution of I was complete. The fractions containing homogeneous I were combined and evaporated to dryness. The residue was recrystallized from H2O; yield 290 mg (34%), mp 265°-267° (Mel-Temp).

情報源と証拠