Reaktion #65347

ord-492f07f3c31d4e92a53dd1a1c1b0a219

Reaktionsgleichung

[K+].[N-]=[N+]=[N-]
potassium azide
Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Thymidine
[K+].[N-]=[N+]=[N-]
potassium azide
Nc1ncnc2nc[nH]c12
Adenine
O=c1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2F)c(=O)[nH]1
1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil
→
Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1F
title compound
Nc1ncnc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1F
9-(2-Deoxy-2-fluoro-β-D-ribofuranosyl)adenine

Edukte

—
purine nucleoside
[K+].[N-]=[N+]=[N-]
potassium azide
Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Thymidine
[K+].[N-]=[N+]=[N-]
potassium azide
Nc1ncnc2nc[nH]c12
Adenine
O=c1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@H]2F)c(=O)[nH]1
1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil

Reagenzien

Keine

Lösungsmittel

O=P([O-])([O-])[O-].[K+].[K+].[K+]
potassium phosphate
O=P([O-])([O-])[O-].[K+].[K+].[K+]
potassium phosphate

Reaktionsbedingungen

Temperatur
37°CELSIUS
Detaillierte Bedingungen
See reaction.notes.procedure_details.

Aufarbeitung

  1. 1
    workup.ADDITION4,381,344) were added
  2. 2
    workup.WAITOn day 6
  3. 3
    workup.WAITOn day 17
  4. 4
    Filtrationthe suspension was filtered
  5. 5
    Sonstigethe filtrate was evaporated
  6. 6
    FiltrationThe suspension was filtered
  7. 7
    WaschenThe product was eluted with water
  8. 8
    workup.ADDITIONProduct containing fractions
  9. 9
    Sonstigethe solvent removed under vacuum
  10. 10
    workup.DISSOLUTIONThe residue was dissolved in water

Vorschrift

Adenine (Mann Research Laboratories, Inc., 0.8 g, 5.9 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 10 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. Thymidine phosphorylase (2,400 I.U.) and purine nucleoside phosphorylase (3,900 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 6, the reaction was diluted to 100 ml with 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. On day 17, the suspension was filtered and the filtrate was evaporated. The residue was suspended in warm water. The suspension was filtered and the filtrate applied to a 1.5×12 cm column of anion exchange resin (Bio-Rad AG1X2-hydroxide form). The product was eluted with water. Product containing fractions were combined and the solvent removed under vacuum. The residue was dissolved in water and lyophilized to obtain the title compound that analyzed as a 0.6 hydrate.

Quelle

DOI: 10.6084/m9.figshare.5104873.v1Patent: US05420115uspto-grants-1995_05