Structure-activity relationship study of 4′-O-methylgrynullarin derivatives for the development of novel anticancer agents based on anti-austerity strategy

4′-O-Methylgrynullarin 1 and its derivatives 2–4 showed preferential cytotoxicity under nutrient-deprived conditions without cytotoxicity under normal-nutrient conditions, indicating that its derivatives might have the potential to lead to novel anti-cancer agents based on anti-austerity strategy. The divergent synthesis of 4′-O-methylgrynullarin derivatives using the Suzuki-Miyaura coupling reaction as a key step and the evaluation of the synthesized derivatives revealed a clear structure-activity relationship. We found that the 6-prenyl moiety and 7-phenolic hydroxy group on the isoflavone skeleton are essential for preferential cytotoxicity, and that even if the substituent groups on C-ring are simpler than those in 1–4, cytotoxicity is maintained to some extent.