Thymidine → 9-(2-Deoxy-2-fluoro-beta-D-ribofuranosyl)-6-ethoxy-9H-purine

HRID 37083

Reaktionsgleichung

Reaktionsgleichung von HRID 37083
[CH2:1]([O:3][C:4]1[N:12]=[CH:11][N:10]=[C:9]2[C:5]=1[NH:6][CH:7]=[N:8]2)[CH3:2].[F:13][C@@H:14]1[C@H:18]([OH:19])[C@@H:17]([CH2:20][OH:21])[O:16][C@H:15]1N1C=CC(=O)NC1=O.[N-]=[N+]=[N-].[K+].[OH-].[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:13][C@@H:14]1[C@H:18]([OH:19])[C@@H:17]([CH2:20][OH:21])[O:16][C@H:15]1[N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][CH:11]=[N:12][C:4]=2[O:3][CH2:1][CH3:2]

Komponenten

7

Edukt 5

HCID 5789Thymidine3×HCID 14797Potassium Hydroxide2×HCID 873386-Ethoxypurine2×HCID 1508512'Fluoro-2'-deoxyuridineHCID 10290740Potassium azide

Produkt 1

HCID 103799129-(2-Deoxy-2-fluoro-beta-D-ribofuranosyl)-6-ethoxy-9H-purine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 62657Potassium Phosphate, TribasicLösungsmittel

Reaktionsbedingungen

Temperatur
37 °C

Versuchsvorschrift

6-Ethoxypurine (Sigma Chemical Company; 0.2 g, 1.2 mmoles) and 1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil (0.4 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 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. The pH of the suspension was adjusted to 7.0 with KOH and thymidine phosphorylase (2,000 I.U.) and purine nucleoside phosphorylase (5,540 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 5, and additional 2,000 I.U. thymidine phosphorylase and 2,770 I.U. of purine nucleoside phosphorylase were added. On day 9, 0.2 g 6-ethoxypurine was added. The pH of the reaction was adjusted to 7.0 with KOH and 2,000 I.U. thymidine phosphorylase and 5,540 I.U. purine nucleoside phosphorylase were added. On day 28, the suspension was filtered. The filtrate was applied to a 2.5×8.5 cm column of anion exchange resin (Bio-Rad AG1X2-hydroxide form). After washing with water, the product was eluted with methanol/water (3/7). Product containing fractions were combined and the solvent removed under vacuum. The product contained in the residue was further purified by chromatography on a 2.5×90 cm column of Biogel P-2 (Bio-Rad) with water/methanol (8/2) as the solvent followed by chromatography on a 2.5×50 cm silica gel column with acetonitrile/water (49/1) as the solvent. Product containing fractions were combined and the solvent removed under vacuum. The residue was dissolved in water and lyophilized to obtain title compound which analyzed as a 0.5 hydrate.

Aufarbeitung

  1. addition4,381,344) were added
  2. waitOn day 5, and additional 2,000 I.U
  3. waitOn day 28
  4. filtrationthe suspension was filtered
  5. washAfter washing with water
  6. washthe product was eluted with methanol/water (3/7)
  7. additionProduct containing fractions
  8. customthe solvent removed under vacuum
  9. customwas further purified by chromatography on a 2.5×90 cm column of Biogel P-2 (Bio-Rad) with water/methanol (8/2) as the solvent
  10. additionProduct containing fractions
  11. customthe solvent removed under vacuum
  12. dissolutionThe residue was dissolved in water

Quellen und Nachweise

ORD-Eintrag
ord-110e8a725dc7486398ddfa211d8dead5
Quelldatensatz
uspto-grants-1995_05
Patentnummer
US05420115

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