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

HRID 37088

Reaktionsgleichung

Reaktionsgleichung von HRID 37088
[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'-fluoroadenosineAusbeute 94,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 62657Potassium Phosphate, TribasicLösungsmittel

Reaktionsbedingungen

Temperatur
37 °C

Versuchsvorschrift

2,6-Diaminopurine (Pacific Chemical Laboratories, 2.0 g, 12.7 mmoles) and 1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil (0.8 g; 3.3 mmoles) which may be prepared according to J. F. Codington et al., (J. Org. Chem. 29:558, 1964) were suspended to 500 ml of 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. Thymidine phosphorylase (41,700 I.U.) and purine nucleoside phosphorylase (83,300 I.U.) (T. A. Krenitsky et al., Biochemistry 20:3615, 1981 and U.S. Pat. No. 4,381,344) which had been absorbed onto 10.5 g of DEAE-cellulose (25 ml) were added and the suspension shaken at 37° C. After 24 hours 2.0 g of 1,6-diaminopurine was added and the temperature increased to 50° C. After another 24 hours the reaction was filtered. The filter cake was washed with water and the filtrates combined and the solvent removed under vacuum. The residue was dissolved in hot water and the pH adjusted to pH 9.4 with NH4OH. The solution was applied to a 2.5×13 cm column of anion exchange resin (Bio-Rad AG1X2-hydroxide form). After washing the column with water, the product was eluted with methanol/water (9/1). Product containing fractions were combined and the solvent removed under vacuum. The residue was treated as above. Product containing fractions were combined and the solvent removed under vacuum. The residue was dissolved in water and lyophilization yielded 0.89 g of title compound that analyzed as a 0.5 hydrate.

Aufarbeitung

  1. custom4,381,344) which had been absorbed onto 10.5 g of DEAE-cellulose (25 ml)
  2. additionwere added
  3. additionAfter 24 hours 2.0 g of 1,6-diaminopurine was added
  4. temperaturethe temperature increased to 50° C
  5. filtrationAfter another 24 hours the reaction was filtered
  6. washThe filter cake was washed with water
  7. customthe solvent removed under vacuum
  8. dissolutionThe residue was dissolved in hot water
  9. washAfter washing the column with water
  10. washthe product was eluted with methanol/water (9/1)
  11. additionProduct containing fractions
  12. customthe solvent removed under vacuum
  13. additionThe residue was treated as above
  14. additionProduct containing fractions
  15. customthe solvent removed under vacuum
  16. dissolutionThe residue was dissolved in water

Quellen und Nachweise

ORD-Eintrag
ord-43de96fd4e664029aee3dccd95cb1512
Quelldatensatz
uspto-grants-1995_05
Patentnummer
US05420115

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