We have discovered a new mode of anticancer action of the natural product ainsliatrimer A

Natural products have played a crucial role in the development of new therapeutic agents. However, the target identification for natural products is still challenging due to the structural complexity and the lack of efficient biochemical methods. In the previous studies, we have accomplished the collective total syntheses of a number of structurally complex and bioactive […]

Natural products have played a crucial role in the development of new therapeutic agents. However, the target identification for natural products is still challenging due to the structural complexity and the lack of efficient biochemical methods. In the previous studies, we have accomplished the collective total syntheses of a number of structurally complex and bioactive oligomeric sesquiterpenoids. (Org. Lett. 2010, 12, 4284；J. Am. Chem. Soc. 2012, 134, 12414; Chem. Sci. 2013, 4, 1163; J. Org. Chem. 2014, 79, 3289).

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) (J. Am. Chem. Soc. 2013, 135, 4996; Highlighted by Chem. & Eng. News 2013, 14, 37), 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.

This latest work was published online recently (Angew. Chem. Int. Ed. 2014，DOI: 10.1002/anie.201407225). Congratulating Chao, Ting and Qiang for this excellent work!

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