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

Chao Li, Ting Dong, Qiang Li, and Xiaoguang Lei*
Angew. Chem. Int. Ed. 2014, 53, 12111-12115

Herein, we report an efficient approach for exploring the novel anti-cancer 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 […]

Herein, we report an efficient approach for exploring the novel anti-cancer 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 the pre-target imaging revealed that PPARγ, a nucleus receptor, was a functional cellular target for ainsliatrimer A. We also confirmed that the anti-cancer activity of ainsliatrimer A was caused by the activation of PPARγ.

http://onlinelibrary.wiley.com/doi/10.1002/anie.201407225/abstract