Thymidine → 2-Amino-2'-deoxy-2'-fluoroadenosine

HRID 37067

Reaktionsgleichung

Reaktionsgleichung von HRID 37067
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([NH2:11])[N:3]=1.[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+]>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:14]2[O:15][C@H:16]([CH2:19][OH:20])[C@@H:17]([OH:18])[C@H:13]2[F:12])=[C:4]([NH2:11])[N:3]=1

Komponenten

6

Edukt 4

HCID 5789ThymidineHCID 309762,6-DiaminopurineHCID 1508512'Fluoro-2'-deoxyuridineHCID 10290740Potassium azide

Produkt 1

HCID 99711012-Amino-2'-deoxy-2'-fluoroadenosine

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 62657Potassium Phosphate, TribasicLösungsmittel

Reaktionsbedingungen

Temperatur
37 °C

Versuchsvorschrift

2,6-Diaminopurine (Pacific Chemical Laboratories, 0.8 g, 4.8 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 50 ml of 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/w) potassium azide. Thymidine phosphorylase (3,850 I.U.) and purine nucleoside phosphorylase (3,760 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 12, the reaction was filtered. The filtrate was applied to a 1.5×15 cm column of anion exchange resin (Bio-Rad AG1X2-hydroxide form). After washing the column with water/methanol (7/3), the product was eluted with water/methanol (1/1). Product containing fractions were combined and the solvent removed under vacuum. The residue was dissolved in water and lyophilized to obtain title compound that analyzed as a 1.2 hydrate.

Aufarbeitung

  1. addition4,381,344) were added
  2. waitOn day 12
  3. filtrationthe reaction was filtered
  4. washAfter washing the column with water/methanol (7/3)
  5. washthe product was eluted with water/methanol (1/1)
  6. additionProduct containing fractions
  7. customthe solvent removed under vacuum
  8. dissolutionThe residue was dissolved in water

Quellen und Nachweise

ORD-Eintrag
ord-2a68bc996c0b4243a4c64ab147797792
Quelldatensatz
uspto-grants-1995_05
Patentnummer
US05420115

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