Thymidine → 2-Amino-9-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)-6-methoxy-9H-purine

HRID 37073

反応式

HRID 37073 の反応式
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([O:11][CH3:12])[N:3]=1.[F:13][C@@H:14]1[C@H:18]([OH:19])[C@@H:17]([CH2:20][OH:21])[O:16][C@H:15]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:15]2[O:16][C@H:17]([CH2:20][OH:21])[C@@H:18]([OH:19])[C@H:14]2[F:13])=[C:4]([O:11][CH3:12])[N:3]=1

参加物

6

反応物 4

HCID 5789Thymidine2 回HCID 65275O-(6)-MethylguanineHCID 1508512'Fluoro-2'-deoxyuridineHCID 10290740Potassium azide3 回

生成物 1

HCID 98827462-Amino-9-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)-6-methoxy-9H-purine

試薬・触媒・溶媒 1

HCID 62657Potassium Phosphate, Tribasic溶媒3 回

反応条件

温度
37 °C

実験手順

2-Amino-6-methoxypurine (0.8 g, 4.8 mmoles) which may be prepared according to R. W. Balsiger and J. A. Montgomery (J. Org. Chem. 20:1573, 1960) 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 10, the reaction was diluted to 200 ml with 5 mm potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. On day 16, 2,640 I.U. of thymidine phosphorylase and 4,360 I.U. of purine nucleoside phosphorylase were added. On day 24, the reaction was filtered and the filtrate was evaporated. The residue was suspended in methanol. The suspension was filtered and the filtrate evaporated. The residue was dissolved in water and applied to a 2.5×7 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). After the solvent was removed under vacuum, the residue was dissolved in water and lyophilized to obtain title compound which analyzed as a 0.5 hydrate.

後処理

  1. addition4,381,344) were added
  2. waitOn day 6
  3. waitOn day 10
  4. waitOn day 16, 2,640 I.U
  5. waitOn day 24
  6. filtrationthe reaction was filtered
  7. customthe filtrate was evaporated
  8. filtrationThe suspension was filtered
  9. customthe filtrate evaporated
  10. dissolutionThe residue was dissolved in water
  11. washAfter washing the column with water
  12. washthe product was eluted with methanol/water (9/1)
  13. customAfter the solvent was removed under vacuum
  14. dissolutionthe residue was dissolved in water

出典と根拠

ORDレコード
ord-0de01bdf3c3c4f4ebdb71e4b467ed52e
出典データセット
uspto-grants-1995_05
特許番号
US05420115

関連ノート

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