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

HRID 1376442ノート

反応式

HRID 1376442 の反応式
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])[N:3]=1.[F:16][C@@H:17]1[C@@H:21]([CH2:22][OH:23])[O:20][C@@H:19](N2C=CC(=O)NC2=O)[CH2:18]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+]>[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:19]2[O:20][C@H:21]([CH2:22][OH:23])[C@@H:17]([F:16])[CH2:18]2)=[C:4]([N:11]([CH2:14][CH3:15])[CH2:12][CH3:13])[N:3]=1

参加物

6

反応物 4

HCID 5789Thymidine2 回HCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178463887HCID 178463887、化合物

生成物 1

HCID 677039762-amino-6-diethylamino-9-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)-9H-purine

試薬・触媒・溶媒 1

HCID 62657Potassium Phosphate, Tribasic溶媒

反応条件

温度
45 °C

実験手順

2-Amino-6-diethylamino-9H-purine (0.47 g 2.3 mmoles) and 2',3'-dideoxy-3'-fluorouridine (0.41 g, 1.8 mmoles) were suspended in potassium phosphate buffer (10 mM) 50 ml), pH 6.8, containing 0.04% potassium azide. Purified purine nucleoside phosphorylase (5350 units) and thymidine phosphorylase (2000 unit (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 14 days, additional purine nucleoside phosphorylase (15,700 units) and thymidine phosphorylase (4000 units) were added to the reaction mixture. After a total reaction time of 123 days, denatured protein was removed by filtration and the filtrate was applied to a column of AG1-X2 (2.5×10 cm, OH- form). After the column was washed with methanol, fractions containing product were pooled, evaporated and chromatographed on silica gel (2.5×20 cm) using dichloromethane:methanol (97:3). Solvent was removed and lyophilization yielded 2-amino-6-diethylamino-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-9H-purine.

後処理

  1. addition4,381,344) were added to the reaction mixture
  2. customAfter a total reaction time of 123 days
  3. customwas removed by filtration
  4. washAfter the column was washed with methanol, fractions
  5. additioncontaining product
  6. customevaporated
  7. customchromatographed on silica gel (2.5×20 cm)
  8. customSolvent was removed

出典と根拠

ORDレコード
ord-f52f3f2a072a493ea12d7555e6fa8a71
出典データセット
uspto-grants-1997_09
特許番号
US05663154

反応ノート

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