Cyclic Depsipeptide BE‐43547A2: Synthesis and Activity against Pancreatic Cancer Stem Cells

Abstract Asymmetric total synthesis of the cyclic depsipeptide BE‐43547A 2 was achieved in 15 linear steps on a 350 mg scale in one batch. The synthesis features the highly diastereoselective construction of an α‐hydroxy‐β‐ketoamide through α‐hydroxylation with a d.r. of up to 86:1. BE‐43547A 2 significantly reduces the percentage of pancreatic cancer stem cells (PCSCs) in Panc‐1 cell cultures, and dramatically reduces the tumorsphere‐forming capability of Panc‐1 cells. An in vivo tumor‐initiation assay, a gold standard for cancer stem cell assays, confirmed that BE‐43547A 2 can abolish the tumorigenesis of Panc‐1 cells. The anti‐PCSC activity of BE‐43547A 2 could make this depsipeptide scaffold a promising starting point for discovering new PCSC‐targeting drugs.