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

HRID 1376446Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1376446
[CH2:1]([NH:7][C:8]1[N:16]=[CH:15][N:14]=[C:13]2[C:9]=1[N:10]=[CH:11][NH:12]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[F:17][C@@H:18]1[C@@H:22]([CH2:23][OH:24])[O:21][C@@H:20](N2C=CC(=O)NC2=O)[CH2:19]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>[F:17][C@@H:18]1[C@@H:22]([CH2:23][OH:24])[O:21][C@@H:20]([N:12]2[CH:11]=[N:10][C:9]3[C:13]2=[N:14][CH:15]=[N:16][C:8]=3[NH:7][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH2:19]1

Komponenten

7

Edukt 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178444747HCID 178444747, Verbindung

Produkt 1

HCID 677039649-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)-6-(hexylamino)-9H-purineAusbeute 29,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 62657Potassium Phosphate, TribasicLösungsmittel

Reaktionsbedingungen

Temperatur
45 °C

Versuchsvorschrift

6-Hexylamino-9H-purine (0.67 g, 2.6 mmoles, Sigma Chemical Company) and 2',3'-dideoxy-3'-fluorouridine (0.50 g, 2.2 mmoles) were suspended in potassium phosphate buffer (50 ml, 10 mM), pH 7.0, containing 0.04% potassium azide. Purine nucleoside phosphorylase (1120 I.U.) and thymidine phosphorylase (10,000 I.U.) (Krenitsky, et al., Biochemistry, 20, 3615 (1981) and U.S. Pat. No. 4,381,344) immobilized on DEAE cellulose was added to the reaction and the suspension was stirred at 45° C. After 4 days, MeOH (175 ml) was added to the reaction. The reaction was applied to a column containing product were pooled, concentrated, and flash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (92:8). Fractions containing product were pooled, concentrated, and then flash chromatographed again on silica gel (2.5×20 cm) with dichloromethane:acetone (9:1). Solvent was removed and lyophilization yielded 9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-(hexylamino)-9H-purine (29%) (0.22 g): mp 83° C.;

Aufarbeitung

  1. additionwas added to the reaction
  2. additioncontaining product
  3. concentrationconcentrated
  4. customflash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (92:8)
  5. additionFractions containing product
  6. concentrationconcentrated
  7. customflash chromatographed again on silica gel (2.5×20 cm) with dichloromethane:acetone (9:1)
  8. customSolvent was removed

Quellen und Nachweise

ORD-Eintrag
ord-2c82d9ad36f847518d4b287323530f1c
Quelldatensatz
uspto-grants-1997_09
Patentnummer
US05663154

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