报告题目：Total Synthesis and medicinal chemistry of Anti-Cancer Stem CellsNatural product BE-43547A2

报 告 人：孙元军 （南开大学）

报告时间：2019年3月21日（星期四）上午9:00

报告地点：药学院云轩楼1323会议室

Yuanjun Sun is pursuing his Ph.D. degree in chemical biology from Nankai University. His Ph.D. work in Nankai University focused on total synthesis of cyclic depsipeptides with high anti-tumor activities. He completed the asymmetrical total synthesis of BE-43547A₂ in 15 linear steps on a 3.2 g scale in one batch. He also achieved the structure modifications of the natural product to improve anti-tumor activities and drug-like properties. Especially, he found that BE-43547A₂ could significantly reduce the percentage of pancreatic cancer stem cells, and ablate the tumorsphere forming capability of Panc-1 cells. The highly productive total synthesis and exciting anti-PCSC activities, along with the unknown mechanism of action, warrant BE-43547A₂ as a promising beginning for the discovery of novel PCSC-targeting drugs.

报告摘要：

The asymmetric total synthesis of cyclic depsipeptide BE-43547A₂ was achieved in 15 linear steps. The synthesis is featured with highly diastereoselective construction of α-hydroxy-β-ketoamide via α-hydroxylation with a d.r. up to 86:1. The details of synthetic efforts that led to the total synthesis of BE-43547A₂ were reported, the final 6 steps were optimized, and the overall yield was improved from 4.5% to 9.7%. The tumor-initiating assay in-vivo, a gold standard for cancer stem cell assays, confirmed BE-43547A₂ could abolish the tumorigenesis of Panc-1 cells. The anti-PCSC activity of BE-43547A₂ will make this depsipeptide scaffold a start for discovering new PCSC-targeting drug.