Trimethylsilyl triflate → 9-(2-O-Acetyl-4-C-acetyloxymethyl-3,5-di-O-benzyl-beta-D-ribofuranosyl)-6-N-benzoyl-adenine

HRID 434279ノート

反応式

HRID 434279 の反応式
[C:1]([O:4][CH2:5][C@:6]1([CH2:27][O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[O:14][CH:9](OC(=O)C)[C@H:8]([O:15][C:16](=[O:18])[CH3:17])[C@@H:7]1[O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)(=[O:3])[CH3:2].[C:36]([NH:44][C:45]1[N:53]=[CH:52][N:51]=[C:50]2[C:46]=1[NH:47][CH:48]=[N:49]2)(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.O([Si](C)(C)C)S(C(F)(F)F)(=O)=O>ClCCl>[C:16]([O:15][C@@H:8]1[C@H:7]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C@@:6]([CH2:5][O:4][C:1](=[O:3])[CH3:2])([CH2:27][O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[O:14][C@H:9]1[N:49]1[CH:48]=[N:47][C:46]2[C:50]1=[N:51][CH:52]=[N:53][C:45]=2[NH:44][C:36](=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)(=[O:18])[CH3:17]

参加物

6

反応物 4

HCID 65367Trimethylsilyl triflateHCID 970756-BenzamidopurineHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 153742654-C-(Acetoxymethyl)-1,2-di-O-acetyl-3,5-di-O-benzyl-D-ribofuranose

生成物 1

HCID 206107969-(2-O-Acetyl-4-C-acetyloxymethyl-3,5-di-O-benzyl-beta-D-ribofuranosyl)-6-N-benzoyl-adenine

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a stirred suspension of the anomeric mixture 33 (5.0 g, 10.3 mmol) and 6-N-benzoyladenine (3.76 g, 15.7 mmol) in anhydrous dichloromethane (200 cm3) was added N,O-bis(trimethylsilyl)acetamide (15.54 cm3, 61.8 mmol). The reaction mixture was stirred at reflux for 1 h and then cooled to room temperature. Trimethylsilyl triflate (7.0 cm3, 38.7 mmol) was added dropwise and the mixture was refluxed for 20 h. The reaction mixture was allowed to cool to room temperature and the volume of the mixture was reduced to ¼ under reduced pressure. Dichloromethane (250 cm3) was added, and the solution was washed with a saturated aqueous solution of sodium hydrogencarbonate (3×50 cm3) and water (50 cm3). The organic phase was dried (Na2SO4) and evaporated under reduced pressure. The residue was purified by silica gel column chromatography using dichloromethane/methanol (99.5:0.5, v/v) as eluent to give nucleoside 58 as white solid material (3.65 g, 52%). δH (CDCl3) 9.25 (1H, br s, NH), 8.71 (1H, s, 8-H), 8.24 (1H, s, 2-H), 8.0 (2H, d, J 7.5, Bz), 7.60-7.23 (13H, m, Bn, Bz), 6.35 (1H, d, J 4.6, 1′-H), 5.99 (1H, dd, J 4.9, 5.3, 2′-H), 4.78 (1H, d, J 5.6, 3′-H), 4.64-4.42 (5H, m, Bn, 1′-Ha), 4.25 (1H, d, J 12.1, 1″-Hb), 3.72 (1H, d, J 10.1, 5′-Ha), 3.56 (1H, d, J 10.1, 5′-Hb), 2.07 (3H, s, COCH3), 2.02 (3H, s, COCH3). δC (CDCl3) 170.42, 169.72 (COCH3), 164.60 (NHCO), 152.51 (C-6), 151.45 (C-2), 149.46 (C-4), 141.88 (C-8), 137.04, 137.00, 133.50, 132.60, 128.86, 128.66, 128.53, 128.41, 128.38, 128.18, 128.06, 127.91, 127.88, 127.79, 127.63, 123.26 (Bz, Bn, C-5), 86.38 (C-1′), 86.25 (C-4′), 77.74, 74.74, 74.44, 73.48 (C-2′, C-3′, 2×Bn), 70.11 (C-1″), 63.42 (C-5′), 20.70, 20.54 (COCH3). FAB-MS m/z 666 [M+H]+.

後処理

  1. temperatureat reflux for 1 h
  2. temperaturethe mixture was refluxed for 20 h
  3. temperatureto cool to room temperature
  4. washthe solution was washed with a saturated aqueous solution of sodium hydrogencarbonate (3×50 cm3) and water (50 cm3)
  5. dry with materialThe organic phase was dried (Na2SO4)
  6. customevaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-4bde57c6f4984707b6b24f633bd33993
出典データセット
uspto-grants-2003_12
特許番号
US06670461B1

反応ノート

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