Thymidine → 2-Amino-9-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)-6-iodo-9H-purine

HRID 37081

Reaktionsgleichung

Reaktionsgleichung von HRID 37081
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([I: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+].[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+].C(O)(=O)C>[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]([I:11])[N:3]=1

Komponenten

8

Edukt 5

HCID 5789Thymidine3×HCID 14797Potassium HydroxideHCID 1508512'Fluoro-2'-deoxyuridineHCID 61015752-Amino-6-iodopurineHCID 10290740Potassium azide2×

Produkt 1

HCID 104083502-Amino-9-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)-6-iodo-9H-purine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidLösungsmittelHCID 62657Potassium Phosphate, TribasicLösungsmittel2×

Reaktionsbedingungen

Temperatur
37 °C

Versuchsvorschrift

2-Amino-6-iodopurine (0.8 g, 3.1 mmoles) which may be prepared according to R. T. Koda et al. (J. Pharm. Sci. 57:2056, 1968) 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. The pH of the suspension was adjusted to 7.2 with KOH. Thymidine phosphorylase (2,000 I.U.) and purine nucleoside phosphorylase (3,250 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 pH of the reaction was adjusted to 6.8 with acetic acid, and 2,000 I.U. of thymidine phosphorylase and 3,250 I.U. of purine nucleoside phosphorylase were added. On day 26, the reaction was diluted to 500 ml with 5 mM potassium phosphate buffer, pH 7, which contained 0.04% (w/v) potassium azide, and 2,000 I.U. thymidine phosphorylase and 3,250 I.U. purine nucleoside phosphorylase were added. On day 40, the reaction was filtered. The filtrate was evaporated. The residue was suspended in water/n-propanol (7/3) and filtered. The filtrate was evaporated. The residue was suspended in methanol and then filtered. The product which was contained in the filtrate was purified by chromatography on a 5×90 cm column of Biogel P-2 (Bio-Rad) with water/n-propanol (7/3) as the solvent, followed by chromatography on a 5×90 cm column of Sephadex G-10 (Pharmacia LKB) whith water/n-propanol (7/3) as the solvent. After the solvent was removed under vacuum, the residue was suspended in water and lyophilized to obtain title compound that analyzed as a 0.6 hydrate.

Aufarbeitung

  1. addition4,381,344) were added
  2. waitOn day 12
  3. waitOn day 26
  4. waitOn day 40
  5. filtrationthe reaction was filtered
  6. customThe filtrate was evaporated
  7. filtrationfiltered
  8. customThe filtrate was evaporated
  9. filtrationfiltered
  10. customwas purified by chromatography on a 5×90 cm column of Biogel P-2 (Bio-Rad) with water/n-propanol (7/3) as the solvent
  11. customAfter the solvent was removed under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-e379e5501b364482ae8569ae05ab17df
Quelldatensatz
uspto-grants-1995_05
Patentnummer
US05420115

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