The Application of Tandem Aza‐Wittig Reaction to Synthesize Artemisinin–Guanidine Hybrids and Their Anti‐Tumor Activity

Abstract Three series of novel artemisinin–guanidine hybrids 4a–4f , 8a–8h and 9a–9h have been facilely synthesized via four‐component reaction (aza‐Wittig reaction) and evaluated for their anti‐tumor activities against A549, HT‐29 and MDA‐MB‐231 cell lines in vitro . All of the tested compounds showed enhanced anti‐tumor activities with IC 50 values ranging from 0.02 µM to 12.0 µM as compared to DHA (dihydroartemisinin). Among them, artemisinin derived dimers, compounds 9b (IC 50 = 0.05 µM), 9d (IC 50 = 0.06 µM) and 9f (IC 50 = 0.02 µM) were found to be most active against HT29 cells.