Ethanol → 7-Methylcamptothecin

Participants

Reaction Steps

Ferrous sulfate heptahydrate (4.17 g, 15 m-mol) and ethanol (3 ml, 60 m-mol) were dissolved in water (30 ml). Camptothecin (700 mg, 2 m-mol) was suspended in the solution and dissolved therein by adding concentrated sulfuric acid (15 ml) in small portions to the suspension. To the mixture was added dropwise under ice-cooling and agitation a 30% aqueous solution of hydrogen peroxide (1.63 ml, 16 m-mol). After addition of the hydrogen peroxide, the mixture was stirred for 6 hours at room temperature. To the reaction mixture was added ferrous sulfate heptahydrate (2.0 g, 7.2 m-mol) and then was added dropwise under ice-cooling and agitation a 30% aqueous solution of hydrogen peroxide (1 ml, 9.8 m-mol). The agitation was continued for 15 hours at room temperature. To complete the reaction, additional ferrous sulfate heptahydrate (4.2 g, 15 m-mol) and a 30% aqueous solution of hydrogen peroxide (1.5 ml, 14.7 m-mol) were added to the reaction mixture and the whole was stirred for 8 hours at room temperature. The reaction mixture was diluted with ice water (2.5 liters) and extracted with chloroform (3 liters). The chloroform layer was dried with anhydrous magnesium sulfate, filtered and evaporated until dryness under reduced pressure. The residue was purified by way of column chromatography (chloroform) through silica gel (10 g) followed by recrystallization from n-hexane-chloroform whereby 127 mg (17.5%) of the objective compound were obtained as yellow needle crystals. M.P. 280°-281° C.

Provenance & Evidence