Proton sponge → 11-O-methyl-geldanamycin

HRID 1814216ノート

反応式

HRID 1814216 の反応式
[CH3:1][C@@H:2]1[CH2:24][C:23]2[C:25](=[O:26])[C:18](=[CH:19][C:20]([C:22]=2[O:27][CH3:28])=[O:21])[NH:17][C:15](=[O:16])[C:14]([CH3:29])=[CH:13][CH:12]=[CH:11][C@H:10]([O:30][CH3:31])[C@@H:9]([O:32][C:33]([NH2:35])=[O:34])[C:8]([CH3:36])=[CH:7][C@H:6]([CH3:37])[C@@H:5]([OH:38])[C@@H:4]([O:39][CH3:40])[CH2:3]1.F[B-](F)(F)F.[CH3:46][O+](C)C.CN(C)C1C2C(=CC=CC=2N(C)C)C=CC=1>ClCCl.C(OCC)(=O)C>[CH3:1][C@@H:2]1[CH2:24][C:23]2[C:25](=[O:26])[C:18](=[CH:19][C:20]([C:22]=2[O:27][CH3:28])=[O:21])[NH:17][C:15](=[O:16])[C:14]([CH3:29])=[CH:13][CH:12]=[CH:11][C@H:10]([O:30][CH3:31])[C@@H:9]([O:32][C:33]([NH2:35])=[O:34])[C:8]([CH3:36])=[CH:7][C@H:6]([CH3:37])[C@@H:5]([O:38][CH3:46])[C@@H:4]([O:39][CH3:40])[CH2:3]1

参加物

6

反応物 3

HCID 88675Proton spongeHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 5288382Geldanamycin

生成物 1

HCID 4414024411-O-methyl-geldanamycin

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
40 °C

実験手順

To a suspension of geldanamycin (1 equiv.) in dichloromethane (20 mL per mmol of geldanamycin) is added trimethyloxonium tetrafluoroborate (3 equiv.) and N, N, N′, N′-tetra-methyinaphthalene-1,8-diamine (3.5 equiv). After stirring at 40° C. for 2 h, the suspension was diluted with ethyl acetate and washed sequentially with 0.1 M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution, and saturated aqueous sodium chloride. The organic solution was dried over anhydrous sodium sulfate, filtered, and evaporated to dryness, giving a brown solid. Purification by flash chromatography on silica gel (eluted using mixed dichloromethane/ethyl acetate/methanol solvents) gave 11-O-methyl-geldanamycin (compound I-e) as a yellow solid. Electrospray ionization time-of-flight mass spectrometry (“ESI TOF MS”) m/z 597.2770, calc'd for C30H42N2O9Na [M+Na]+, 597.2783. 13C NMR (CDCl3, 100 MHz)δ (relative to CDCl3 at 77.0 ppm) 12.2, 13.9, 16.0, 21.5, 29.5, 32.5, 33.7, 36.5, 56.2, 57.4, 59.4, 61.5, 78.9, 79.4, 81.7, 83.3, 111.0, 125.7, 128.1, 130.5, 131.9, 134.5, 136.6, 137.8, 155.9, 156.9, 168.6, 183.9, 184.1.

後処理

  1. washwashed sequentially with 0.1 M aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution, and saturated aqueous sodium chloride
  2. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customgiving a brown solid
  6. customPurification by flash chromatography on silica gel (eluted using mixed dichloromethane/ethyl acetate/methanol solvents)

出典と根拠

ORDレコード
ord-58bbbae53c974afc97b67faddd2345d3
出典データセット
uspto-grants-2005_04
特許番号
US06875863B1

反応ノート

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