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

HRID 1376446노트

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HRID 1376446 반응식
[CH2:1]([NH:7][C:8]1[N:16]=[CH:15][N:14]=[C:13]2[C:9]=1[N:10]=[CH:11][NH:12]2)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[F:17][C@@H:18]1[C@@H:22]([CH2:23][OH:24])[O:21][C@@H:20](N2C=CC(=O)NC2=O)[CH2:19]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>[F:17][C@@H:18]1[C@@H:22]([CH2:23][OH:24])[O:21][C@@H:20]([N:12]2[CH:11]=[N:10][C:9]3[C:13]2=[N:14][CH:15]=[N:16][C:8]=3[NH:7][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH2:19]1

참가 물질

7

반응물 4

HCID 5789ThymidineHCID 1624502',3'-Dideoxy-3'-fluorouridineHCID 10290740Potassium azideHCID 178444747HCID 178444747, 화합물

생성물 1

HCID 677039649-(2,3-dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)-6-(hexylamino)-9H-purine수율 29.6%

시약·촉매·용매 2

HCID 887Methanol용매HCID 62657Potassium Phosphate, Tribasic용매

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온도
45 °C

실험 절차

6-Hexylamino-9H-purine (0.67 g, 2.6 mmoles, Sigma Chemical Company) and 2',3'-dideoxy-3'-fluorouridine (0.50 g, 2.2 mmoles) were suspended in potassium phosphate buffer (50 ml, 10 mM), pH 7.0, containing 0.04% potassium azide. Purine nucleoside phosphorylase (1120 I.U.) and thymidine phosphorylase (10,000 I.U.) (Krenitsky, et al., Biochemistry, 20, 3615 (1981) and U.S. Pat. No. 4,381,344) immobilized on DEAE cellulose was added to the reaction and the suspension was stirred at 45° C. After 4 days, MeOH (175 ml) was added to the reaction. The reaction was applied to a column containing product were pooled, concentrated, and flash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (92:8). Fractions containing product were pooled, concentrated, and then flash chromatographed again on silica gel (2.5×20 cm) with dichloromethane:acetone (9:1). Solvent was removed and lyophilization yielded 9-(2,3-dideoxy-3-fluoro-β-D-erythro-pentofuranosyl)-6-(hexylamino)-9H-purine (29%) (0.22 g): mp 83° C.;

후처리

  1. additionwas added to the reaction
  2. additioncontaining product
  3. concentrationconcentrated
  4. customflash chromatographed on silica gel (2.5×20 cm) with dichloromethane:acetone (92:8)
  5. additionFractions containing product
  6. concentrationconcentrated
  7. customflash chromatographed again on silica gel (2.5×20 cm) with dichloromethane:acetone (9:1)
  8. customSolvent was removed

출처 및 근거

ORD 기록
ord-2c82d9ad36f847518d4b287323530f1c
출처 데이터셋
uspto-grants-1997_09
특허 번호
US05663154

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