Thymidine → (2R,3R,4R,5R)-5-(2-Amino-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-ol

HRID 37070

反応式

HRID 37070 の反応式
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[CH:4][N:3]=1.[F:11][C@@H:12]1[C@H:16]([OH:17])[C@@H:15]([CH2:18][OH:19])[O:14][C@H:13]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+].O>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:13]2[O:14][C@H:15]([CH2:18][OH:19])[C@@H:16]([OH:17])[C@H:12]2[F:11])=[CH:4][N:3]=1

参加物

7

反応物 4

HCID 5789Thymidine2 回HCID 99552-AminopurineHCID 1508512'Fluoro-2'-deoxyuridineHCID 10290740Potassium azide

生成物 1

HCID 10355712(2R,3R,4R,5R)-5-(2-Amino-9H-purin-9-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-ol

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 62657Potassium Phosphate, Tribasic溶媒

反応条件

温度
37 °C

実験手順

2-Aminopurine (Vega Biochemicals, 0.4 g, 3.0 mmoles) and 1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil (0.2 g, 0.71 mmoles) which may be prepared according to J. F. Codington et al. (J. Org. Chem. 29:558, 1964) were suspended in 35 ml of 5 mM potassium phosphate buffer, pH 7.0, which contained 0.04% (w/v) potassium azide. Thymidine phosphorylase (1,930 I.U.) and purine nucleoside phosphorylase (1,880 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 24, the reaction was diluted to 200 ml with water and 1,390 I.U. of thymidine phosphorylase, and, 1,880 I.U. of purine nucleoside phosphorylase were added. On day 35, the suspension was evaporated. The residue was dissolved in water/methanol (7/3) and applied to a 1.5×15 cm column of anion exchange resin (Bio-Rad AG1X2-hydroxide form). The product was eluted with water/methanol (7/3). The product-containing fractions were combined and the solvent removed under vacuum. The residue was dissolved 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 24
  3. waitOn day 35
  4. customthe suspension was evaporated
  5. dissolutionThe residue was dissolved in water/methanol (7/3)
  6. washThe product was eluted with water/methanol (7/3)
  7. customthe solvent removed under vacuum
  8. dissolutionThe residue was dissolved in water

出典と根拠

ORDレコード
ord-807e87e254e04a6e86e8e198ff4b36c6
出典データセット
uspto-grants-1995_05
特許番号
US05420115

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