Total Synthesis of 4’-O-Methylgrynullarin and Related Isoflavone Natural Products

Isoflavones containing several hydroxyl groups are known to exhibit a variety of biological activities. 4’-O-Methylgrynullarin 1 and its derivatives 2–4 were isolated from Derris scandens flowers and their structures were determined by Suresh and co-workers in 2021. Because 4’-O-methylgrynullarin 1 showed preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, 1 has the potential to become a novel anti-cancer drug based on an anti-austerity strategy. We achieved the total synthesis of 4’-O-methylgrynullarin 1 and its derivatives 2–4 using Suzuki-Miyaura coupling of the prenylated iodochromones 14 and 16 with the corresponding phenylboronic acids 25, 27, and 31 as the key step.