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

HRID 613776Notes

Reaction equation

HRID 613776 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.CS(O)(=O)=O.O>CC(C)=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 4

HCID 876(+-)-MethionineHCID 962WaterHCID 6395Methanesulfonic AcidHCID 10607Podophyllotoxin

Product 1

HCID 122797(-)-4'-Demethylepipodophyllotoxin

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A solution of 50 g (0.12 mol) of podophyllotoxin I, prepared in 50 ml of acetone, is added with stirring at ordinary temperature to a mixture consisting of 100 g (0.67 mol) of D,L-methionine, of 500 ml (7.7 mol) of methanesulfonic acid and of 10 ml of water. The temperature rises to approximately 40° C. and stirring is maintained for 2 h with return to ambient temperature. The mixture is then poured onto ice in order to obtain a precipitate which is extracted with ethyl acetate (3×700 ml). The organic phases are washed with an NaHCO3 solution and then separated by settling, dried over Na2SO4, filtered and evaporated under reduced pressure in order to obtain 4'-demethylepipodophyllotoxin, existing in the form of a white solid. 45 g (Yd 94%) are obtained.

Workup

  1. additionis added
  2. customrises to approximately 40° C.
  3. stirringstirring
  4. additionThe mixture is then poured onto ice in order
  5. customto obtain a precipitate which
  6. extractionis extracted with ethyl acetate (3×700 ml)
  7. washThe organic phases are washed with an NaHCO3 solution
  8. customseparated
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. customevaporated under reduced pressure in order

Sources & evidence

ORD record
ord-2504db1eb8964f899c4a392884571edf
Source dataset
uspto-grants-1999_12
Patent number
US06008382

Reaction notes

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