Formaldehyde → Irofulven

HRID 1611463Notes

Reaction equation

HRID 1611463 reaction equation
OS(O)(=O)=O.[CH2:6]=[O:7].[CH3:8][C:9]1[C:18]2([CH2:20][CH2:19]2)[C@:17]([OH:22])([CH3:21])[C:15](=[O:16])[C:14]2[C:10]=1[C@@H:11](O)[C@@:12](CO)([CH3:23])[CH:13]=2>CC(C)=O>[CH3:23][C:12]1[CH:13]=[C:14]2[C:10](=[C:9]([CH3:8])[C:18]3([C@:17]([OH:22])([CH3:21])[C:15]2=[O:16])[CH2:20][CH2:19]3)[C:11]=1[CH2:6][OH:7]

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 1118Sulfuric AcidHCID 344200(2′S,3′R,6′R)-2′,3′-Dihydro-3′,6′-dihydroxy-2′-(hydroxymethyl)-2′,4′,6′-trimethylspiro[cyclopropane-1,5′-[5H]inden]-7′(6′H)-one

Product 1

HCID 148189IrofulvenYield 24.3%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of 250 ml of 1M H2SO4 and 200 ml acetone was added 40 g paraformaldehyde (MW 30, 1.33 mol). The solution was heated to clear and was then allowed to cool to room temperature. 1 g illudin S (MW 264, 3.79 mmol) was added to the above solution. The mixture was stirred at room temperature for 72 h and was partitioned between ethyl acetate and water. The organic extracts were washed by saturated NaHCO3 and saline respectively to neutral. After being dried by MgSO4, the solution was concentrated and chromatographed to give 245 mg 14 (23.4%) and 226 mg HMAF (24.3%). 14 is a white crystal: mp 100.5-102.5; IR (KBr) 3469, 2966, 2858, 1703, 1656, 1596, 1172 cm−1; 1H NMR (CDCl3) δ 0.48 (m, 1H), 0.84 (m, 1H), 0.99 (m, 1H), 1.10 (s, 3H), 1.17 (m, 1H), 1.32 (s, 3H), 1.67 (s, 3H), 3.61 (s, 1H), 3.73 (d, J=11.7 Hz, 1H), 3.96 (d, J=11.7 Hz, 1H), 4.56 (s, 1H), 4.75 (d, J=5.4 Hz, 1H), 4.91 (d, J=5.4 Hz, 1H), 6.52 (s, 1H); 13C NMR (CDCl3) δ 199.7, 141.4, 136.5, 135.9, 134.7, 90.0, 80.3 75.9, 70.8, 46.8, 32.3, 24.7, 22.5, 13.8, 8.9, 5.6; MS m/z 276 (M+), 217, 201, 173; HRMS for C16H20O4 calcd 276.1362. found 276.1364. UV λmax 305 nm (ε 3148).

Workup

  1. temperatureThe solution was heated to clear and
  2. customwas partitioned between ethyl acetate and water
  3. washThe organic extracts were washed by saturated NaHCO3 and saline respectively to neutral
  4. dry with materialAfter being dried by MgSO4
  5. concentrationthe solution was concentrated
  6. customchromatographed

Sources & evidence

ORD record
ord-b4f44f25fe3a437d8bc710d3fc643823
Source dataset
uspto-grants-2006_01
Patent number
US06987193B2

Reaction notes

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