The role of the 12-carboxylic acid group in the spontaneous autoxidation of dihydroartemisinic acid

Article abstract of DOI:10.1016/S0040-4020(01)01192-9

Three of the four steps in the slow spontaneous autoxidation of dihydroartemisinic acid to artemisinin ('ene-type' reaction of molecular oxygen with the Δ^4,5 double bond, Hock cleavage of the resulting tertiary allylic hydroperoxide, oxygenation of the enol product from Hock cleavage and cyclization of the resulting vicinal hydroperoxyl-aldehyde to the 1,2,4-trioxane system of artemisinin) are shown to be assisted by the proximity of the 12-carboxylic acid functional group in dihydroartemisinic acid to the functional groups participating in these reactions.