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

HRID 1376441Notes

Reaction equation

HRID 1376441 reaction equation
[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

Participants

7

Reactant 4

HCID 5789Thymidine2×HCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178420435HCID 178420435, compound

Product 1

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

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-e321e9c7dafe4f8ca60edb17234db579
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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