Thymidine → 6-benzylmercapto-9-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)-9H-purine

HRID 1376441Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1376441
[CH2:1]([S:8][C:9]1[N:17]=[CH:16][N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][NH:13]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:18][C@@H:19]1[C@@H:23]([CH2:24][OH:25])[O:22][C@@H:21](N2C=CC(=O)NC2=O)[CH2:20]1.[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+].CO>[CH2:1]([S:8][C:9]1[N:17]=[CH:16][N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[C@@H:21]1[O:22][C@H:23]([CH2:24][OH:25])[C@@H:19]([F:18])[CH2:20]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

7

Edukt 4

HCID 5789Thymidine2×HCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178420435HCID 178420435, Verbindung

Produkt 1

HCID 867511916-benzylmercapto-9-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)-9H-purineAusbeute 81,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 62657Potassium Phosphate, TribasicLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

6-Benzylmercapto-9H-purine (0.49 g, 2.0 mmoles, Sigma Chemical Company) and 2',3'-dideoxy-3'-fluorouridine (0.32 g, 1.4 mmoles) were suspended in potassium phosphate buffer (10 mM) 100 ml), pH 6.8, containing 0.04% potassium azide. Purified purine nucleoside phosphorylase (1070 I.U.) and thymidine phosphorylase (400 I.U.) (Krenitsky et al., Biochemistry, 20, 3615 (1981) and U.S. Pat. No. 4,381,344) were added to the reaction mixture and the suspension stirred at 45° C. After 3 days, additional purine nucleoside phosphorylase (10,700 I.U.) and thymidine phosphorylase (4000 I.U.) were added. Four days later, methanol was added to the reaction mixture to precipitate protein. The protein was removed by filtration and the filtrate applied to a series of coupled columns. The first column contained AG1 resin (2.5×10 cm, OH- form) and the second column contained XAD resin (2.5×20 cm). The columns were washed with water 300 ml and the product removed with methanol. Product fractions were pooled and solvent was removed in vacuo. The residue was flash chromatographed on silica gel (2.5×20 cm) using chloroform:methanol (199:1). Solvent was removed and lyophilization yielded 6-benzylmercapto-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-9H-purine (0.41 g).

Aufarbeitung

  1. addition4,381,344) were added to the reaction mixture
  2. customto precipitate protein
  3. customThe protein was removed by filtration
  4. washThe columns were washed with water 300 ml
  5. customthe product removed with methanol
  6. customsolvent was removed in vacuo
  7. customchromatographed on silica gel (2.5×20 cm)
  8. customSolvent was removed

Quellen und Nachweise

ORD-Eintrag
ord-e321e9c7dafe4f8ca60edb17234db579
Quelldatensatz
uspto-grants-1997_09
Patentnummer
US05663154

Notizen zur Reaktion

Wird geladen…