Ingenol → (4S,5R,6R,18R)-4,5-dihydroxy-3,8,8,15,15,18-hexamethyl-7,9-dioxapentacyclo[11.5.1.01,5.06,11.014,16]nonadeca-2,11-dien-19-one

HRID 1050908Notes

Reaction equation

HRID 1050908 reaction equation
[CH3:1][C@H:2]1[C@:14]23[CH:17]=[C:18]([CH3:21])[C@H:19]([OH:20])[C@@:13]2([OH:22])[C@H:12]([OH:23])[C:11]([CH2:24][OH:25])=[CH:10][C@H:9]([C:15]3=[O:16])[C@@H:5]2[C:6]([CH3:8])([CH3:7])[C@@H:4]2[CH2:3]1.C([O-])(O)=O.[Na+].O.[C:32]1(C)[CH:37]=CC(S(O)(=O)=O)=C[CH:33]=1>CC(C)=O>[CH3:1][C@H:2]1[C:14]23[CH:17]=[C:18]([CH3:21])[C@H:19]([OH:20])[C@@:13]2([OH:22])[C@H:12]2[C:11]([CH2:24][O:25][C:32]([CH3:37])([CH3:33])[O:23]2)=[CH:10][CH:9]([C:15]3=[O:16])[CH:5]2[C:6]([CH3:8])([CH3:7])[CH:4]2[CH2:3]1

Participants

5

Reactant 3

HCID 442042IngenolHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 91827745(4S,5R,6R,18R)-4,5-dihydroxy-3,8,8,15,15,18-hexamethyl-7,9-dioxapentacyclo[11.5.1.01,5.06,11.014,16]nonadeca-2,11-dien-19-oneYield 69%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Ingenol (1.00 g, 2.30 mmol) was dissolved in a solution of p-toluenesulphonic acid monohydrate in acetone (0.47 mg/mL, 22.5 mL). The solution was stirred at room temperature for 25 min. To this solution was added a saturated aqueous solution of NaHCO3 (0.2 mL). The obtained mixture was concentrated in vacuo. The residue was taken up in brine and extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (heptane/ethyl acetate 19:1→heptane/ethyl acetate 0:1), giving the title compound as a white solid (616 mg, 69%). (See also: Opferkuch, H. J. et.al., Z. Naturforsch., (1981), 86b, 878-887.)

Workup

  1. concentrationThe obtained mixture was concentrated in vacuo
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined organic phases were dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography (heptane/ethyl acetate 19:1→heptane/ethyl acetate 0:1)

Sources & evidence

ORD record
ord-a6d4822c18634a50861df33b640d16cc
Source dataset
uspto-grants-2016_07
Patent number
US09388124B2

Reaction notes

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