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Thymidine → (2R,3R,4R,5R)-5-(2-Amino-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-ol

HRID 37089
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 37089
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[CH:4][N:3]=1.[F:11][C@@H:12]1[C@H:16]([OH:17])[C@@H:15]([CH2:18][OH:19])[O:14][C@H:13]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:13]2[O:14][C@H:15]([CH2:18][OH:19])[C@@H:16]([OH:17])[C@H:12]2[F:11])=[CH:4][N:3]=1
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Komponenten

6

Edukt 4

HCID 5789ThymidineHCID 99552-AminopurineHCID 1508512'Fluoro-2'-deoxyuridineHCID 10290740Potassium azide

Produkt 1

HCID 10355712(2R,3R,4R,5R)-5-(2-Amino-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-olAusbeute 92,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 62657
Potassium Phosphate, Tribasic
Lösungsmittel

Reaktionsbedingungen

Temperatur
37 °C

Versuchsvorschrift

2-Aminopurine (Pacific Chemical Laboratories, 3.0 g, 22.2 mmoles) and 1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil (0.5 g; 2.0 mmoles) which may be prepared according to J. F. Codington et al., (J. Org. Chem. 29:558, 1964) were suspended in 25 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 3.0 g of 2,6-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 suspended in water and filtered. The filter cake was extracted with water (25° C.) until no product remained in the filter cake. The filtrates were combined, the pH was adjusted to pH 9.4 with NH4OH, and the solution applied to a 2.5×20 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 dissolved in chloroform/methanol/water (75:25:4) and applied to a 5×25 cm column of silica gel 60. The product was eluted with chloroform/methanl/water (75:25:4). Product containing fractions were combined and the solvent removed under vacuum. The residue was dissolved in hot water and filtered through a 0.22 μm-pore membrane filter. Lyophilization of the filtrate yielded 0.50 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 3.0 g of 2,6-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. filtrationfiltered
  9. extractionThe filter cake was extracted with water (25° C.) until no product
  10. washAfter washing the column with water
  11. washthe product was eluted with methanol/water (9/1)
  12. additionProduct containing fractions
  13. customthe solvent removed under vacuum
  14. dissolutionThe residue was dissolved in chloroform/methanol/water (75:25:4)
  15. washThe product was eluted with chloroform/methanl/water (75:25:4)
  16. additionProduct containing fractions
  17. customthe solvent removed under vacuum
  18. dissolutionThe residue was dissolved in hot water
  19. filtrationfiltered through a 0.22 μm-pore membrane
  20. filtrationfilter

Quellen und Nachweise

ORD-Eintrag
ord-9d7ca476fb82440080fbc6eeb46f8715
Quelldatensatz
uspto-grants-1995_05
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US05420115

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