Thymidine → adenosine, 2'-deoxy-2'-fluoro-N-methyl-

HRID 37082Notes

Reaction equation

HRID 37082 reaction equation
[CH3:1][NH:2][C:3]1[N:11]=[CH:10][N:9]=[C:8]2[C:4]=1[NH:5][CH:6]=[N:7]2.[F:12][C@@H:13]1[C@H:17]([OH:18])[C@@H:16]([CH2:19][OH:20])[O:15][C@H:14]1N1C=CC(=O)NC1=O.[N-]=[N+]=[N-].[K+].[C@@H]1(N2C=C(C)C(=O)NC2=O)O[C@H](CO)[C@@H](O)C1>P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[F:12][C@@H:13]1[C@H:17]([OH:18])[C@@H:16]([CH2:19][OH:20])[O:15][C@H:14]1[N:7]1[CH:6]=[N:5][C:4]2[C:8]1=[N:9][CH:10]=[N:11][C:3]=2[NH:2][CH3:1]

Participants

6

Reactant 4

HCID 5789ThymidineHCID 67955N6-MethyladenineHCID 1508512'Fluoro-2'-deoxyuridineHCID 10290740Potassium azide2×

Product 1

HCID 14654364adenosine, 2'-deoxy-2'-fluoro-N-methyl-

Reagents, catalysts & solvents 1

HCID 62657Potassium Phosphate, TribasicSolvent2×

Conditions

Temperature
37 °C

Procedure

6-Methylaminopurine (Sigma Chemical Company, 0.8 g, 5.4 mmoles) and 1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil (0.39 g, 1.6 mmoles) which may be prepared according to J. F. Codington et al. (J. Org. Chem. 29:558, 1964) were suspended in 20 ml of 10 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. Thymidine phosphorylase (2,400 I.U.) and purine nucleoside phosphorylase (3,900 I.U.) (T. A. Krenitsky et al., Biochemistry 20:3615, 1981 and U.S. Pat. No. 4,381,344) were added and the suspension stirred at 37° C. On day 6, the reaction was diluted to 100 ml with 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. On day 17, the reaction was filtered. The filtrate was evaporated. The residue was suspended in methanol and then filtered. The filtrate was evaporated. The residue was dissolved in water and applied to a 2.5×7 cm column of anion exchange resin (Bio-Rad AG1X2-hydroxide form). The product was eluted with water. Product-containing fractions were combined and the solvent removed under vacuum. The residue was dissolved in water and filtered through a 0.2 μm-pore membrane filter. Lyophilization of the filtrate yielded title compound.

Workup

  1. addition4,381,344) were added
  2. waitOn day 6
  3. waitOn day 17
  4. filtrationthe reaction was filtered
  5. customThe filtrate was evaporated
  6. filtrationfiltered
  7. customThe filtrate was evaporated
  8. dissolutionThe residue was dissolved in water
  9. washThe product was eluted with water
  10. customthe solvent removed under vacuum
  11. dissolutionThe residue was dissolved in water
  12. filtrationfiltered through a 0.2 μm-pore membrane
  13. filtrationfilter

Sources & evidence

ORD record
ord-1e92ca6e797c4b038c1cdf832851d55e
Source dataset
uspto-grants-1995_05
Patent number
US05420115

Reaction notes

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