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Cyclic Depsipeptide BE‐43547A 2 : Synthesis and Activity against Pancreatic Cancer Stem Cells
Author(s) -
Sun Yuanjun,
Ding Yahui,
Li Dongmei,
Zhou Ruifei,
Su Xiuwen,
Yang Juan,
Guo Xiaoqian,
Chong Chuanke,
Wang Jinghan,
Zhang Weicheng,
Bai Cuigai,
Wang Liang,
Chen Yue
Publication year - 2017
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201709744
Subject(s) - depsipeptide , cancer stem cell , stem cell , pancreatic cancer , cancer research , in vivo , chemistry , cancer cell , carcinogenesis , hydroxylation , cancer , biochemistry , biology , microbiology and biotechnology , genetics , enzyme , gene
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.