Thymidine → (2R,3R,4S,5R)-5-(2,6-diaminopurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol

HRID 1682085

Reaktionsgleichung

Reaktionsgleichung von HRID 1682085
[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=C(C)C(=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>[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 72327FmauHCID 10290740Potassium azide

Produkt 1

HCID 460081(2R,3R,4S,5R)-5-(2,6-diaminopurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-olAusbeute 58,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 5462222PotassiumLösungsmittel

Reaktionsbedingungen

Temperatur
37 °C

Versuchsvorschrift

2,6-Diaminopurine (Pacific Chemical Laboratories, 1.0 g, 6.4 mmoles) and 1-(2-Deoxy-2-fluoro-β-D-arabinofuranosyl)thymine (C. H. Tann et al., J. Org. Chem. 50:3647, 1985; 0.3 g, 1.2 mmoles) was suspended in 100 ml of 5 mM potassium phsophate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. Thymidine phosphorylase (160,000 I.U.) and purine nucleoside phosphorylase (290,000 I.U.) (T. A. Krenitsky et al., Biochemistry, 20:3615, 1981 and U.S. Pat. No. 4,381,444) absorbed onto 69 ml of DEAE-cellulose were added and the suspension shaken at 37° C. for 1 day. The suspension was then shaken at 50° C. for 1 day at which time 2.0 g of 2,6-diaminopurine was added. After shaking for 4 additional days at 50° C., 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 water and applied to a 2.5×17 cm AG1X2-hydroxide (Bio-Rad) column. After washing the column with water, the product was eluted with methanol/water (9/1). The product was further purified by chromatography on silica gel with acetonitrile/water (9/1) as the solvent followed by chromatography on silica gel with chloroform/methanol/water (80/20/2) as the solvent. After the solvent was removed under vacuum, the residue was dissolved in water and lyophilization yielded 0.2 g of title compound that analysed as a 1.4 hydrate.

Aufarbeitung

  1. custom4,381,444) absorbed onto 69 ml of DEAE-cellulose
  2. additionwere added
  3. stirringThe suspension was then shaken at 50° C. for 1 day at which time 2.0 g of 2,6-diaminopurine
  4. additionwas added
  5. stirringAfter shaking for 4 additional days at 50° C.
  6. filtrationthe reaction was filtered
  7. washThe filter cake was washed with water
  8. customthe solvent removed under vacuum
  9. dissolutionThe residue was dissolved in water
  10. washAfter washing the column with water
  11. washthe product was eluted with methanol/water (9/1)
  12. customThe product was further purified by chromatography on silica gel with acetonitrile/water (9/1) as the solvent
  13. customAfter the solvent was removed under vacuum
  14. dissolutionthe residue was dissolved in water

Quellen und Nachweise

ORD-Eintrag
ord-c5cf61ac8f8c44b199cd69dfcd07b15d
Quelldatensatz
uspto-grants-1992_12
Patentnummer
US05175274

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