Cyclic Depsipeptide BE‐43547A2: Synthesis and Activity against Pancreatic Cancer Stem Cells
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 r...
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| Veröffentlicht in: | Angewandte Chemie International Edition 2017-11, Vol.56 (46), p.14627-14631 |
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| creator | 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 |
| description | 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.
BE the best: Total synthesis of the cyclic depsipeptide BE‐43547A2 was achieved in 15 linear steps. BE‐43547A2 was shown to reduce the percentage of cancer stem cells in pancreatic cancer cell cultures by 21‐fold. In a tumorsphere‐formation assay, the number of tumorspheres formed in the BE‐43547A2‐treated group was about 46‐fold less than that in the doxycycline‐treated group. A murine tumor‐initiation assay confirmed that BE‐43547A2 can abolish tumorigenesis. |
| doi_str_mv | 10.1002/anie.201709744 |
| format | Article |
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BE the best: Total synthesis of the cyclic depsipeptide BE‐43547A2 was achieved in 15 linear steps. BE‐43547A2 was shown to reduce the percentage of cancer stem cells in pancreatic cancer cell cultures by 21‐fold. In a tumorsphere‐formation assay, the number of tumorspheres formed in the BE‐43547A2‐treated group was about 46‐fold less than that in the doxycycline‐treated group. A murine tumor‐initiation assay confirmed that BE‐43547A2 can abolish tumorigenesis.</description><edition>International ed. in English</edition><identifier>ISSN: 1433-7851</identifier><identifier>EISSN: 1521-3773</identifier><identifier>DOI: 10.1002/anie.201709744</identifier><language>eng</language><publisher>Weinheim: Wiley Subscription Services, Inc</publisher><subject>Cancer ; cancer stem cells ; cyclic depsipeptides ; Drug delivery ; Drugs ; Hydroxylation ; Pancreatic cancer ; Stem cells ; Synthesis ; total synthesis ; Tumorigenesis</subject><ispartof>Angewandte Chemie International Edition, 2017-11, Vol.56 (46), p.14627-14631</ispartof><rights>2017 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-1317-7097</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fanie.201709744$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fanie.201709744$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids></links><search><creatorcontrib>Sun, Yuanjun</creatorcontrib><creatorcontrib>Ding, Yahui</creatorcontrib><creatorcontrib>Li, Dongmei</creatorcontrib><creatorcontrib>Zhou, Ruifei</creatorcontrib><creatorcontrib>Su, Xiuwen</creatorcontrib><creatorcontrib>Yang, Juan</creatorcontrib><creatorcontrib>Guo, Xiaoqian</creatorcontrib><creatorcontrib>Chong, Chuanke</creatorcontrib><creatorcontrib>Wang, Jinghan</creatorcontrib><creatorcontrib>Zhang, Weicheng</creatorcontrib><creatorcontrib>Bai, Cuigai</creatorcontrib><creatorcontrib>Wang, Liang</creatorcontrib><creatorcontrib>Chen, Yue</creatorcontrib><title>Cyclic Depsipeptide BE‐43547A2: Synthesis and Activity against Pancreatic Cancer Stem Cells</title><title>Angewandte Chemie International Edition</title><description>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.
BE the best: Total synthesis of the cyclic depsipeptide BE‐43547A2 was achieved in 15 linear steps. BE‐43547A2 was shown to reduce the percentage of cancer stem cells in pancreatic cancer cell cultures by 21‐fold. In a tumorsphere‐formation assay, the number of tumorspheres formed in the BE‐43547A2‐treated group was about 46‐fold less than that in the doxycycline‐treated group. A murine tumor‐initiation assay confirmed that BE‐43547A2 can abolish tumorigenesis.</description><subject>Cancer</subject><subject>cancer stem cells</subject><subject>cyclic depsipeptides</subject><subject>Drug delivery</subject><subject>Drugs</subject><subject>Hydroxylation</subject><subject>Pancreatic cancer</subject><subject>Stem cells</subject><subject>Synthesis</subject><subject>total synthesis</subject><subject>Tumorigenesis</subject><issn>1433-7851</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNpdkL1OwzAUhS0EEqWwMltiYUnxvx22EApUqgCpXVFkYqe4StMQu6BsPALPyJPgqqgD0z1X97tHRweAc4xGGCFypRtnRwRhiVLJ2AEYYE5wQqWkh1EzShOpOD4GJ94vI68UEgPwkvdl7Up4a1vvWtsGZyy8Gf98fTPKmczINZz1TXiz3nmoGwOzMrgPF3qoF9o1PsBn3ZSd1SGa5FHaDs6CXcHc1rU_BUeVrr09-5tDML8bz_OHZPp0P8mzabIgWLHEEGVNKmVFJFelEVRoQkWVYoOI5RzH02tFCK6kVpiUlTGKCok4jc9SWDoElzvbtlu_b6wPxcr5MgbQjV1vfIFTpiTnkqmIXvxDl-tN18RwkRKYUqoEj1S6oz5dbfui7dxKd32BUbFtutg2XeybLrLHyXi_0V_i7XKf</recordid><startdate>20171113</startdate><enddate>20171113</enddate><creator>Sun, Yuanjun</creator><creator>Ding, Yahui</creator><creator>Li, Dongmei</creator><creator>Zhou, Ruifei</creator><creator>Su, Xiuwen</creator><creator>Yang, Juan</creator><creator>Guo, Xiaoqian</creator><creator>Chong, Chuanke</creator><creator>Wang, Jinghan</creator><creator>Zhang, Weicheng</creator><creator>Bai, Cuigai</creator><creator>Wang, Liang</creator><creator>Chen, Yue</creator><general>Wiley Subscription Services, Inc</general><scope>7TM</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1317-7097</orcidid></search><sort><creationdate>20171113</creationdate><title>Cyclic Depsipeptide BE‐43547A2: Synthesis and Activity against Pancreatic Cancer Stem Cells</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g2184-d28ed977f2758cd636a236f91d02e551977bf221f7a812cfdd836705318476e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Cancer</topic><topic>cancer stem cells</topic><topic>cyclic depsipeptides</topic><topic>Drug delivery</topic><topic>Drugs</topic><topic>Hydroxylation</topic><topic>Pancreatic cancer</topic><topic>Stem cells</topic><topic>Synthesis</topic><topic>total synthesis</topic><topic>Tumorigenesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Yuanjun</creatorcontrib><creatorcontrib>Ding, Yahui</creatorcontrib><creatorcontrib>Li, Dongmei</creatorcontrib><creatorcontrib>Zhou, Ruifei</creatorcontrib><creatorcontrib>Su, Xiuwen</creatorcontrib><creatorcontrib>Yang, Juan</creatorcontrib><creatorcontrib>Guo, Xiaoqian</creatorcontrib><creatorcontrib>Chong, Chuanke</creatorcontrib><creatorcontrib>Wang, Jinghan</creatorcontrib><creatorcontrib>Zhang, Weicheng</creatorcontrib><creatorcontrib>Bai, Cuigai</creatorcontrib><creatorcontrib>Wang, Liang</creatorcontrib><creatorcontrib>Chen, Yue</creatorcontrib><collection>Nucleic Acids Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Angewandte Chemie International Edition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Yuanjun</au><au>Ding, Yahui</au><au>Li, Dongmei</au><au>Zhou, Ruifei</au><au>Su, Xiuwen</au><au>Yang, Juan</au><au>Guo, Xiaoqian</au><au>Chong, Chuanke</au><au>Wang, Jinghan</au><au>Zhang, Weicheng</au><au>Bai, Cuigai</au><au>Wang, Liang</au><au>Chen, Yue</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cyclic Depsipeptide BE‐43547A2: Synthesis and Activity against Pancreatic Cancer Stem Cells</atitle><jtitle>Angewandte Chemie International Edition</jtitle><date>2017-11-13</date><risdate>2017</risdate><volume>56</volume><issue>46</issue><spage>14627</spage><epage>14631</epage><pages>14627-14631</pages><issn>1433-7851</issn><eissn>1521-3773</eissn><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.
BE the best: Total synthesis of the cyclic depsipeptide BE‐43547A2 was achieved in 15 linear steps. BE‐43547A2 was shown to reduce the percentage of cancer stem cells in pancreatic cancer cell cultures by 21‐fold. In a tumorsphere‐formation assay, the number of tumorspheres formed in the BE‐43547A2‐treated group was about 46‐fold less than that in the doxycycline‐treated group. A murine tumor‐initiation assay confirmed that BE‐43547A2 can abolish tumorigenesis.</abstract><cop>Weinheim</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1002/anie.201709744</doi><tpages>5</tpages><edition>International ed. in English</edition><orcidid>https://orcid.org/0000-0002-1317-7097</orcidid></addata></record> |
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| subjects | Cancer cancer stem cells cyclic depsipeptides Drug delivery Drugs Hydroxylation Pancreatic cancer Stem cells Synthesis total synthesis Tumorigenesis |
| title | Cyclic Depsipeptide BE‐43547A2: Synthesis and Activity against Pancreatic Cancer Stem Cells |
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