Proton sponge → 11-O-methyl-geldanamycin

HRID 23870

Reaction equation

HRID 23870 reaction equation
[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

Participants

6

Reactant 3

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

Product 1

HCID 4414024411-O-methyl-geldanamycin

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

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-methylnaphthalene-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.

Workup

  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)

Sources & evidence

ORD record
ord-e979b2581da74b8ea03f9203643b4495
Source dataset
uspto-grants-2005_02
Patent number
US06855705B1

Linked notes

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