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

HRID 1376444Notes

Reaction equation

HRID 1376444 reaction equation
[NH2:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([S:11][CH2:12][CH2:13][CH3:14])[N:3]=1.[F:15][C@@H:16]1[C@@H:20]([CH2:21][OH:22])[O:19][C@@H:18](N2C=CC(=O)NC2=O)[CH2:17]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:18]2[O:19][C@H:20]([CH2:21][OH:22])[C@@H:16]([F:15])[CH2:17]2)=[C:4]([S:11][CH2:12][CH2:13][CH3:14])[N:3]=1

Participants

6

Reactant 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178460807HCID 178460807, compound

Product 1

HCID 677039792-amino-6-propylthio-9-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)-9H-purineYield 30.5%

Reagents, catalysts & solvents 1

HCID 62657Potassium Phosphate, TribasicSolvent

Conditions

Temperature
45 °C

Procedure

2-Amino-6-propylthio-9H-purine (0.29 g 1.4 mmoles) and 2',3'-dideoxy-3'-fluorouridine (0.39 g, 1.7 mmoles) were suspended in potassium phosphate buffer (10 mM) 90 ml), pH 6.8, containing 0.04% potassium azide. Purified purine nucleoside phosphorylase (370 I.U., PNP) and thymidine phosphorylase (TPase) (Krenitsky et al., Biochemistry, 20, 3615 (1981) and U.S. Pat. No. 4,381,444) adsorbed on to DEAE-cellulose were added to The reaction mixture and the suspension stirred at 45° C. After 2 days, additional PNP (370 I.U.) and TPase adsorbed onto DEAE-cellulose was added. The next day the reaction was filtered to remove the immobilized protein and fresh PNP (2700 I.U.) and TPase (1000 I.U.) was added. After 4 days, additional free PNP (2700 I.U.) and TPase (1000 I.U.) was added to the reaction mixture. After 3 days, PNP (5400 I.U.) and TPase (2000 I.U.) were added. After a total of 14 days, solvent was removed in vacuo and the residue was flash chromatographed on silica gel (2.5×23 cm) using CH2Cl2 :MeOH (97:3). Product-containing fractions were pooled and rechromatographed on a second silica gel column (2.5×20 cm) using CHCl3 :MeOH (199:1). Solvent was removed and lyophilization yielded 2-amino-6-propylthio-9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-9H-purine (0.14 g).

Workup

  1. additionwere added to The reaction mixture
  2. additionwas added
  3. filtrationThe next day the reaction was filtered
  4. customto remove the immobilized protein and fresh PNP (2700 I.U.) and TPase (1000 I.U.)
  5. additionwas added
  6. waitAfter 4 days
  7. additionadditional free PNP (2700 I.U.) and TPase (1000 I.U.) was added to the reaction mixture
  8. waitAfter 3 days
  9. additionPNP (5400 I.U.) and TPase (2000 I.U.) were added
  10. customAfter a total of 14 days, solvent was removed in vacuo
  11. customchromatographed on silica gel (2.5×23 cm)
  12. customrechromatographed on a second silica gel column (2.5×20 cm)
  13. customSolvent was removed

Sources & evidence

ORD record
ord-d5b25a4911c944d08021012be9b1cbcc
Source dataset
uspto-grants-1997_09
Patent number
US05663154

Reaction notes

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