Proton sponge → 11-O-methyl-geldanamycin

HRID 2180219

Reaktionsgleichung

Reaktionsgleichung von HRID 2180219
[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

Komponenten

6

Edukt 3

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

Produkt 1

HCID 4414024411-O-methyl-geldanamycin

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

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′-tetramethylnaphthalene-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.

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-f0af49563e504891b9783d634f7e09e0
Quelldatensatz
uspto-grants-2005_05
Patentnummer
US06887993B1

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