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

HRID 37081

反応式

HRID 37081 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]([I: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=CC(=O)NC1=O.[N-]=[N+]=[N-].[K+].[OH-].[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+].C(O)(=O)C>[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]([I:11])[N:3]=1

参加物

8

反応物 5

HCID 5789Thymidine3 回HCID 14797Potassium HydroxideHCID 1508512'Fluoro-2'-deoxyuridineHCID 61015752-Amino-6-iodopurineHCID 10290740Potassium azide2 回

生成物 1

HCID 104083502-Amino-9-(2-deoxy-2-fluoro-beta-D-ribofuranosyl)-6-iodo-9H-purine

試薬・触媒・溶媒 2

HCID 176Acetic Acid溶媒HCID 62657Potassium Phosphate, Tribasic溶媒2 回

反応条件

温度
37 °C

実験手順

2-Amino-6-iodopurine (0.8 g, 3.1 mmoles) which may be prepared according to R. T. Koda et al. (J. Pharm. Sci. 57:2056, 1968) and 1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil (0.39 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. The pH of the suspension was adjusted to 7.2 with KOH. Thymidine phosphorylase (2,000 I.U.) and purine nucleoside phosphorylase (3,250 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 12, the pH of the reaction was adjusted to 6.8 with acetic acid, and 2,000 I.U. of thymidine phosphorylase and 3,250 I.U. of purine nucleoside phosphorylase were added. On day 26, the reaction was diluted to 500 ml with 5 mM potassium phosphate buffer, pH 7, which contained 0.04% (w/v) potassium azide, and 2,000 I.U. thymidine phosphorylase and 3,250 I.U. purine nucleoside phosphorylase were added. On day 40, the reaction was filtered. The filtrate was evaporated. The residue was suspended in water/n-propanol (7/3) and filtered. The filtrate was evaporated. The residue was suspended in methanol and then filtered. The product which was contained in the filtrate was purified by chromatography on a 5×90 cm column of Biogel P-2 (Bio-Rad) with water/n-propanol (7/3) as the solvent, followed by chromatography on a 5×90 cm column of Sephadex G-10 (Pharmacia LKB) whith water/n-propanol (7/3) as the solvent. After the solvent was removed under vacuum, the residue was suspended in water and lyophilized to obtain title compound that analyzed as a 0.6 hydrate.

後処理

  1. addition4,381,344) were added
  2. waitOn day 12
  3. waitOn day 26
  4. waitOn day 40
  5. filtrationthe reaction was filtered
  6. customThe filtrate was evaporated
  7. filtrationfiltered
  8. customThe filtrate was evaporated
  9. filtrationfiltered
  10. customwas purified by chromatography on a 5×90 cm column of Biogel P-2 (Bio-Rad) with water/n-propanol (7/3) as the solvent
  11. customAfter the solvent was removed under vacuum

出典と根拠

ORDレコード
ord-e379e5501b364482ae8569ae05ab17df
出典データセット
uspto-grants-1995_05
特許番号
US05420115

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