Probing the Anticancer Mechanism of (-)-Ainsliatrimer A through Diverted Total Synthesis and Bioorthogonal Ligation

Herein, we report an efficient approach for exploring the novel anticancer mechanism of (-)-ainsliatrimer A, a structurally complex and unique trimeric sesquiterpenoid, through a combined strategy of diverted total synthesis (DTS) and bioorthogonal ligation (TQ ligation), which allowed us to visualize the subcellular localization of this natural product in live cells. Further biochemical studies facilitated by pretarget imaging revealed that PPAR gamma, a nucleus receptor, was a functional cellular target of ainsliatrimer A. We also confirmed that the anticancer activity of ainsliatrimer A was caused by the activation of PPAR gamma.