(+-)-Methionine → (-)-4'-Demethylepipodophyllotoxin

HRID 613774Notes

Reaction equation

HRID 613774 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C@H:13]2[C@H:22]3[C:23]([O:25][CH2:26][C@@H:21]3[C@@H:20]([OH:27])[C:19]3[CH:18]=[C:17]4[O:28][CH2:29][O:30][C:16]4=[CH:15][C:14]2=3)=[O:24])[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9]C.NC(C(O)=O)CCSC.O>FC(F)(F)C(O)=O.CS(O)(=O)=O>[CH3:12][O:11][C:7]1[CH:6]=[C:5]([C@H:13]2[C@H:22]3[C:23]([O:25][CH2:26][C@@H:21]3[C@H:20]([OH:27])[C:19]3[CH:18]=[C:17]4[O:28][CH2:29][O:30][C:16]4=[CH:15][C:14]2=3)=[O:24])[CH:4]=[C:3]([O:2][CH3:1])[C:8]=1[OH:9]

Participants

6

Reactant 3

HCID 876(+-)-MethionineHCID 962WaterHCID 10607Podophyllotoxin

Product 1

HCID 122797(-)-4'-DemethylepipodophyllotoxinYield 95.2%

Reagents, catalysts & solvents 2

HCID 6395Methanesulfonic AcidSolvent2×HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

100 g (0.24 mol) of podophyllotoxin I are dissolved in 186 ml of trifluoroacetic acid with stirring. After cooling the reaction mixture to 0° C., a solution of 198 g (1.32 mol) of D,L-methionine in 500 ml of methanesulfonic acid is introduced, the reaction mixture being maintained between 10 and 20° C. 200 ml of methanesulfonic acid are added to the mixture, which is kept stirring for 1 h at this temperature. The reaction mixture is poured with stirring onto 4 l of water and of ice and the product precipitates. It is extracted with ethyl acetate (3×1 l ). The combined organic phases are washed with an NaHCO3 solution and then dried over Na2SO4, filtered and evaporated under reduced pressure in order to obtain 91.5 g (Yd 94%) of crude 4'-demethylepipodophyllotoxin.

Workup

  1. temperaturethe reaction mixture being maintained between 10 and 20° C
  2. stirringis kept stirring for 1 h at this temperature
  3. additionThe reaction mixture is poured
  4. customthe product precipitates
  5. extractionIt is extracted with ethyl acetate (3×1 l )
  6. washThe combined organic phases are washed with an NaHCO3 solution
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated under reduced pressure in order

Sources & evidence

ORD record
ord-70acee477bae47a08a7967ddd7944711
Source dataset
uspto-grants-1999_12
Patent number
US06008382

Reaction notes

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