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

HRID 1376441노트

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HRID 1376441 반응식
[CH2:1]([S:8][C:9]1[N:17]=[CH:16][N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][NH:13]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:18][C@@H:19]1[C@@H:23]([CH2:24][OH:25])[O:22][C@@H:21](N2C=CC(=O)NC2=O)[CH2:20]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>[CH2:1]([S:8][C:9]1[N:17]=[CH:16][N:15]=[C:14]2[C:10]=1[N:11]=[CH:12][N:13]2[C@@H:21]1[O:22][C@H:23]([CH2:24][OH:25])[C@@H:19]([F:18])[CH2:20]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

참가 물질

7

반응물 4

HCID 5789Thymidine2회HCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178420435HCID 178420435, 화합물

생성물 1

HCID 867511916-benzylmercapto-9-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)-9H-purine수율 81.3%

시약·촉매·용매 2

HCID 887Methanol용매HCID 62657Potassium Phosphate, Tribasic용매

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온도
45 °C

실험 절차

6-Benzylmercapto-9H-purine (0.49 g, 2.0 mmoles, Sigma Chemical Company) and 2',3'-dideoxy-3'-fluorouridine (0.32 g, 1.4 mmoles) were suspended in potassium phosphate buffer (10 mM) 100 ml), pH 6.8, containing 0.04% potassium azide. Purified purine nucleoside phosphorylase (1070 I.U.) and thymidine phosphorylase (400 I.U.) (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 3 days, additional purine nucleoside phosphorylase (10,700 I.U.) and thymidine phosphorylase (4000 I.U.) were added. Four days later, methanol was added to the reaction mixture to precipitate protein. The protein was removed by filtration and the filtrate applied to a series of coupled columns. The first column contained AG1 resin (2.5×10 cm, OH- form) and the second column contained XAD resin (2.5×20 cm). The columns were washed with water 300 ml and the product removed with methanol. Product fractions were pooled and solvent was removed in vacuo. The residue was flash chromatographed on silica gel (2.5×20 cm) using chloroform:methanol (199:1). Solvent was removed and lyophilization yielded 6-benzylmercapto-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-9H-purine (0.41 g).

후처리

  1. addition4,381,344) were added to the reaction mixture
  2. customto precipitate protein
  3. customThe protein was removed by filtration
  4. washThe columns were washed with water 300 ml
  5. customthe product removed with methanol
  6. customsolvent was removed in vacuo
  7. customchromatographed on silica gel (2.5×20 cm)
  8. customSolvent was removed

출처 및 근거

ORD 기록
ord-e321e9c7dafe4f8ca60edb17234db579
출처 데이터셋
uspto-grants-1997_09
특허 번호
US05663154

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