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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence