Medicine and Health Sciences Commons^™

Structure–Activity Relationships Of The Antimalarial Agent Artemisinin 10. Synthesis And Antimalarial Activity Of Enantiomers Of Rac-5Β-Hydroxy-D-Secoartemisinin And Analogs: Implications Regarding The Mechanism Of Action, Mohamed Jahan, Francisco Leon, Frank R. Fronczek, Khaled M. Elokely

Faculty and Student Publications

An efficient synthesis of rac-6-desmethyl-5β–hydroxy-D-secoartemisinin 2, a tricyclic analog of R-(+)-artemisinin 1, was accomplished and the racemate was resolved into the (+)-2b and (−)-2a enantiomers via their Mosher Ester diastereomers. Antimalarial activity resided with only the artemisinin-like enantiomer R-(−)-2a. Several new compounds 9–16, 19a, 19b, 22 and 29 were synthesized from rac-2 but the C-5 secondary hydroxyl group was surprisingly unreactive. For example, the formation of carbamates and Mitsunobu reactions were unsuccessful. In order to assess the unusual reactivity of 2, a single crystal X-ray crystallographic analysis revealed a close intramolecular hydrogen bond from the C-5 alcohol to the oxepane …