Thymidine → 9-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)-6-(hexylamino)-9H-purine

Participants

Reaction Conditions

Reaction Steps

6-Hexylamino-9H-purine (0.67 g, 2.6 mmoles, Sigma Chemical Company) and 2',3'-dideoxy-3'-fluorouridine (0.50 g, 2.2 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.) (Krenitsky, et al., Biochemistry, 20, 3615 (1981) and U.S. Pat. No. 4,381,344) immobilized on DEAE cellulose was added to the reaction and the suspension was stirred at 45° C. After 4 days, MeOH (175 ml) was added to the reaction. The reaction was applied to a column containing product were pooled, concentrated, and flash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (92:8). Fractions containing product were pooled, concentrated, and then flash chromatographed again on silica gel (2.5×20 cm) with dichloromethane:acetone (9:1). Solvent was removed and lyophilization yielded 9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-(hexylamino)-9H-purine (29%) (0.22 g): mp 83° C.;

Provenance & Evidence