9-epi-Artemisinin - How a Single Stereo Center Affects Chemical Reactivity under Reductive Conditions

9-epi-Artemisinin occurs as a minor by-product when artemisinin is obtained from natural or semi-synthetic sources. The preparation of beta-artemether from artemisinin by reduction with sodium borohydride proceeds normally even when the 9-epimer is present. However, the 9-epimer undergoes rearrangement to peroxy acetals. The results are ascribed to the different stabilities of the corresponding dihydro-intermediates due to steric hindrance as suggested by quantum mechanical calculations.