Singlet oxygen artemisinin synthesis

The biosynthesis of artemisinin3 is of interest in that it provides clues to the chemical synthesis of artemisinin from its more abundant precursor in A. annua, artemisinic acid 2. Conjugate reduction of the acrylate double bond of 2 followed by singlet oxygenation leads,... 

Peter Seeberger at the Max-Planck-Institute of Colloids and Interfaces in Potsdam accomplished in 2012 a comparable synthesis, where dihydroartemisinic acid is converted to artemisinin in a flow apparatus with photochemically produced singlet oxygen. [480]... 

Schmid and Hofheinz described an important application of this reaction to the total synthesis of the antimalarial drug artemisinin. The key step in the (-)-isopulegol-based synthesis is the ene-reaction of singlet oxygen with an enol ether (Scheme 12). This reaction leads to an allylic hydroperoxide 20 when the reaction is performed in the nonpolar solvent, CHjClj. The use of the more polar, protic methanol inverts the regioselectivity, and the a-hydroperoxy acetal 21 is formed (presumably by trapping of an intermediary 1,4-zwitterion), which is cycHzed to the target molecule 22 by acid catalysis. 

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