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

Yuanjun Sun; Yahui Ding; Dongmei Li; Ruifei Zhou; Xiuwen Su; Juan Yang; Xiaoqian Guo; Chuanke Chong; Jinghan Wang; Weicheng Zhang; Cuigai Bai; Liang Wang; Yue Chen

doi:10.1002/anie.201709744

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

Yuanjun Sun
, Yahui Ding
, Dongmei Li
, Ruifei Zhou
, Xiuwen Su
, Juan Yang
, Xiaoqian Guo
, Chuanke Chong
, Jinghan Wang
, Weicheng Zhang
, Cuigai Bai
, Liang Wang^*
, Yue Chen

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

Asymmetric total synthesis of the cyclic depsipeptide BE-43547A₂ 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-43547A₂ 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-43547A₂ can abolish the tumorigenesis of Panc-1 cells. The anti-PCSC activity of BE-43547A₂ could make this depsipeptide scaffold a promising starting point for discovering new PCSC-targeting drugs.

Original language	English
Pages (from-to)	14627-14631
Number of pages	5
Journal	Angewandte Chemie - International Edition
Volume	56
Issue number	46
DOIs	https://doi.org/10.1002/anie.201709744
Publication status	Published - 13 Nov 2017
Externally published	Yes

Keywords

cancer stem cells
cyclic depsipeptides
hydroxylation
pancreatic cancer
total synthesis

Access to Document

10.1002/anie.201709744

Cite this

@article{107919b5b4fb49eeb85f022fea440c83,

title = "Cyclic Depsipeptide BE-43547A2: Synthesis and Activity against Pancreatic Cancer Stem Cells",

abstract = "Asymmetric total synthesis of the cyclic depsipeptide BE-43547A2 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-43547A2 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-43547A2 can abolish the tumorigenesis of Panc-1 cells. The anti-PCSC activity of BE-43547A2 could make this depsipeptide scaffold a promising starting point for discovering new PCSC-targeting drugs.",

keywords = "cancer stem cells, cyclic depsipeptides, hydroxylation, pancreatic cancer, total synthesis",

author = "Yuanjun Sun and Yahui Ding and Dongmei Li and Ruifei Zhou and Xiuwen Su and Juan Yang and Xiaoqian Guo and Chuanke Chong and Jinghan Wang and Weicheng Zhang and Cuigai Bai and Liang Wang and Yue Chen",

note = "Publisher Copyright: {\textcopyright} 2017 Wiley-VCH Verlag GmbH \& Co. KGaA, Weinheim.",

year = "2017",

month = nov,

day = "13",

doi = "10.1002/anie.201709744",

language = "English",

volume = "56",

pages = "14627--14631",

journal = "Angewandte Chemie - International Edition",

issn = "1433-7851",

publisher = "John Wiley \& Sons, Ltd",

number = "46",

}

TY - JOUR

T1 - Cyclic Depsipeptide BE-43547A2

T2 - Synthesis and Activity against Pancreatic Cancer Stem Cells

AU - Sun, Yuanjun

AU - Ding, Yahui

AU - Li, Dongmei

AU - Zhou, Ruifei

AU - Su, Xiuwen

AU - Yang, Juan

AU - Guo, Xiaoqian

AU - Chong, Chuanke

AU - Wang, Jinghan

AU - Zhang, Weicheng

AU - Bai, Cuigai

AU - Wang, Liang

AU - Chen, Yue

PY - 2017/11/13

Y1 - 2017/11/13

N2 - Asymmetric total synthesis of the cyclic depsipeptide BE-43547A2 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-43547A2 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-43547A2 can abolish the tumorigenesis of Panc-1 cells. The anti-PCSC activity of BE-43547A2 could make this depsipeptide scaffold a promising starting point for discovering new PCSC-targeting drugs.

AB - Asymmetric total synthesis of the cyclic depsipeptide BE-43547A2 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-43547A2 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-43547A2 can abolish the tumorigenesis of Panc-1 cells. The anti-PCSC activity of BE-43547A2 could make this depsipeptide scaffold a promising starting point for discovering new PCSC-targeting drugs.

KW - cancer stem cells

KW - cyclic depsipeptides

KW - hydroxylation

KW - pancreatic cancer

KW - total synthesis

UR - https://www.scopus.com/pages/publications/85032943163

U2 - 10.1002/anie.201709744

DO - 10.1002/anie.201709744

M3 - Article

C2 - 28984401

AN - SCOPUS:85032943163

SN - 1433-7851

VL - 56

SP - 14627

EP - 14631

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 46

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this