Divergent Total\nSynthesis of Isoflavone Natural Products\nand Their Potential as Therapeutic Agents for TTR Amyloidosis

We have achieved the divergent total\nsynthesis of nine isoflavone\nnatural products <b>1</b>–<b>9</b> starting from\ncommercially available 2,4,6-trihydroxyacetophenone as a starting\nmaterial. The isoflavone skeleton of <b>1</b>–<b>9</b> was constructed by the Suzuki–Miyaura coupling reaction as\nthe key reaction. Investigation of the potential of <b>1</b>–<b>9</b> as therapeutic agents for transthyretin (TTR)\namyloidosis revealed that millexatin F (<b>3</b>) showed the\nbest efficacy in <i>ex vivo</i> competitive binding experiments\nand thioflavin-T fluorescence studies. Therefore, millexatin F (<b>3</b>) is promising as a seed compound for a novel TTR amyloidosis\ntherapeutic agent.