Cyclische Peroxide nach dem Vorbild der Natur: Neue Phenol-abgeleitete bicyclische Peroxide mit mittleren Ringgrößen und Artesunatderivate

Known for over 2000 years in Chinese folk medicine and isolated from the plant artemisia annua in 1972, artemisinin is the best-known cyclic peroxide with pharmacological properties. The potency of artemisinin as anti-cancer drug and the ability to rapidly kill the malaria parasite highly motivates the research for novel analogues. In this work, two synthetic routes to cyclic peroxides were pursued: On the one hand, the artemisinin skeleton was converted into artesunate derivatives by the reaction of dihydroartemisinin with carboxylic acid anhydrides and on the other hand, low-molecular cyclic 1,2,4-trioxo-compounds were synthesized. The second way required the introduction of the peroxide and a subsequent peroxyacetalization reaction. Both reactions did not show good yields in the past, so that a further part of this work consisted in the optimization of these synthesis steps. The phenol-derived bicyclic 1,2,4-trioxo-compounds, which had medium ring sizes, showed interesting conformational properties. This was intensively investigated using quantum chemical calculations (in gas phase), 2D NMR analysis (in solution) and X-ray crystal structures (in solid phase).