Thymidine → 2-amino-6-cyclobutoxy-9-(2,3-dideoxy-3-fluoro-beta-D-erythropentofuranosyl)-9H-purine

Participants

Reaction Conditions

Reaction Steps

2-Amino-6-cyclobutoxy-9H-purine (0.50 g, 2.4 mmoles) and 2'3'-dideoxy-3'-fluorouridine (0.67 g, 2.9 mmoles) were suspended in potassium phosphate buffer (50 ml, 10 mM), pH 7.0, containing 0.04% potassium azide. Purine nucleoside phosphorylase (1120 I.U.) and thymidine phosphorylase (10,000 I.U.) immobilized on DEAE cellulose was added to the reaction and the suspension was stirred at 45° C. After 8 days, MeOH (150 ml) was added to the reaction. The reaction was applied to a column containing AG1-X2 (OH- form, 2.5×10 cm) and eluted with MeOH. Fractions containing product were pooled, concentrated, and flash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (92:8) as eluant. Solvent was removed and lyophilization yielded 0.57 g of 2-amino-6-cyclobutoxy-9-(2,3-dideoxy-3-fluoro-β-D-erythropentofuranosyl)-9H-purine (70%): mp 139°-140° C.;

Provenance & Evidence