Thymine → 1(2-O-Acetyl5-O-benzoyl-4-C-benzoyloxymethyl-3-O-benzyl-beta-D-xylofuranosyl)thymine

HRID 1827443ノート

反応式

HRID 1827443 の反応式
[C:1]([O:9][C@H:10](CO)[C@@:11]1([CH2:32][O:33][C:34](=[O:41])[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:19][CH:14](OC(=O)C)[C@H:13]([O:20][C:21](=[O:23])[CH3:22])[C@H:12]1[O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH:44]1[CH:52]=[C:50]([CH3:51])[C:48](=[O:49])[NH:47][C:45]1=[O:46].C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O.C(=O)([O-])O.[Na+]>C(#N)C>[C:21]([O:20][C@@H:13]1[C@@H:12]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:11]([CH2:32][O:33][C:34](=[O:41])[C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)([CH2:10][O:9][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[O:19][C@H:14]1[N:44]1[CH:52]=[C:50]([CH3:51])[C:48](=[O:49])[NH:47][C:45]1=[O:46])(=[O:23])[CH3:22]

参加物

7

反応物 5

HCID 1135ThymineHCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 235791165-O-Benzoyl-4-C-Benzoyloxymethyl-3-O-Benzyl-1,2-Di-O-Acetyl-D-Glucofuranose

生成物 1

HCID 107940411(2-O-Acetyl5-O-benzoyl-4-C-benzoyloxymethyl-3-O-benzyl-beta-D-xylofuranosyl)thymine収率 85%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
60 °C

実験手順

To a stirred suspension of the anomeric mixture 3 (7.26 g, 0.013 mol) and thymine (3.25 g, 0.028 mol) in anhydrous acetonitrile (80 cm3) was added N,O-bis(trimethylsilyl)acetamide (19.1 cm3, 0.077 mol). The reaction mixture was stirred at 60° C. for 1 h and then cooled to 0° C. Trimethylsilyl triflate (4.1 cm3, 0.023 mol) was added drop-wise during 10 min and the mixture was subsequently heated for 22 h under reflux. After cooling to room temperature, a saturated aqueous solution of sodium hydrogen carbonate (30 cm3) was added and extraction was performed using dichloromethane (100 cm3×3). The combined organic phase was washed with saturated aqueous solutions of sodium hydrogen carbonate (30 cm3×3) and brine (50 cm3×3), dried (Na2SO4) and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using dichloromethane/methanol (0.5–2.0% methanol, v/v) as eluent to give nucleoside 4 (6.88 g, 85%) as a white solid material after evaporation of the solvents under reduced pressure. δH (CDCl3) 8.97 (1H, br s), 8.04–7.23 (16H, m), 6.37 (1H, d, J 3.6), 5.42 (1H, t, J 3.1), 4.89–4.56 (6H, m), 4.22 (1H, d, J 2.6), 2.13 (3H, s), 1.74 (1H, d, J 0.8) δC (CDCl3) 169.9, 166.0, 165.7, 163.4, 150.4, 136.2, 135.2, 133.5, 133.4, 129.8, 129.7, 129.6, 129.5, 129.0, 128.6, 128.4, 128.2, 112.0, 87.4, 86.0, 81.3, 80.3, 72.6, 63.1, 82.9, 20.8, 12.3. FAB-MS m/z 629 [M+H]+. Found (%) C, 64.4; H, 4.9; N, 4.4; C34H32N2O10,0.25H2O requires C, 64.5; H, 5.1; N, 4.4.

後処理

  1. temperaturecooled to 0° C
  2. temperaturethe mixture was subsequently heated for 22 h
  3. temperatureunder reflux
  4. temperatureAfter cooling to room temperature
  5. extractionextraction
  6. washThe combined organic phase was washed with saturated aqueous solutions of sodium hydrogen carbonate (30 cm3×3) and brine (50 cm3×3)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-e5d9315e36494d3d9a6481d17173813e
出典データセット
uspto-grants-2006_05
特許番号
US07053207B2

反応ノート

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