Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck-Suzuki reaction

The synthesis of a previously undescribed sp -rich 6-5-5-6 tetracyclic ring scaffold using a palladium catalysed domino Heck-Suzuki reaction is reported. This reaction is high-yielding, selective for the domino process over the direct Suzuki reaction and tolerant towards a variety of boronic acids....

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Chemical science (Cambridge) 2015-01, Vol.6 (1), p.390-396
Hauptverfasser:	Alza, Esther, Laraia, Luca, Ibbeson, Brett M, Collins, Súil, Galloway, Warren R J D, Stokes, Jamie E, Venkitaraman, Ashok R, Spring, David R
Format:	Artikel
Sprache:	eng
Schlagworte:	Chemistry
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

container_end_page	396
container_issue	1
container_start_page	390
container_title	Chemical science (Cambridge)
container_volume	6
creator	Alza, Esther Laraia, Luca Ibbeson, Brett M Collins, Súil Galloway, Warren R J D Stokes, Jamie E Venkitaraman, Ashok R Spring, David R
description	The synthesis of a previously undescribed sp -rich 6-5-5-6 tetracyclic ring scaffold using a palladium catalysed domino Heck-Suzuki reaction is reported. This reaction is high-yielding, selective for the domino process over the direct Suzuki reaction and tolerant towards a variety of boronic acids. The novel scaffold can also be accessed domino Heck-Stille and radical cyclisations. Compounds based around this scaffold were found to be effective antimitotic agents in a human cancer cell line. Detailed phenotypic profiling showed that the compounds affected the congression of chromosomes to give mitotic arrest and apoptotic cell death. Thus, a novel structural class of antimitotic agents that does not disrupt the tubulin network has been identified.
doi_str_mv	10.1039/c4sc02547d
format	Article
fullrecord	<record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5586250</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1945723413</sourcerecordid><originalsourceid>FETCH-LOGICAL-c378t-8703a440308710985251d33829941a2a5df81547ec05f340568445890ef25103</originalsourceid><addsrcrecordid>eNpVkVtr3DAQhUVJaEKyL_kBRY8l4FZXW34plG0uhUAedt-FIo-zamTJkeQN219f57Y08zID5-PMDAehM0q-UcLb71ZkS5gUTfcJHTMiaFVL3h7sZ0aO0CLnP2QuzqlkzWd0xFRb100tj9G02oWygewyjj02OMQteDxGv7M7653FyYV7nK3p--g7_OTKBptQ3OBKLLM8pjhCKg4y3jozG2TwYIvbAu7i4ELE12AfqtX0d3pwOIGZtRhO0WFvfIbFWz9B68uL9fK6urm9-r38eVNZ3qhSqYZwIwThRDWUtEoySTvOFWtbQQ0zsusVnV8HS2TPBZG1EkKqlkA_k4SfoB-vtuN0N0BnIZRkvB6TG0za6Wic_qgEt9H3caulVDWTzwZf3wxSfJwgFz24bMF7EyBOWdNWyIZxQfmMnr-iNsWcE_T7NZTo56T0UqyWL0n9muEv_x-2R99z4f8AU16PYw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1945723413</pqid></control><display><type>article</type><title>Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck-Suzuki reaction</title><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>PubMed Central Open Access</source><creator>Alza, Esther ; Laraia, Luca ; Ibbeson, Brett M ; Collins, Súil ; Galloway, Warren R J D ; Stokes, Jamie E ; Venkitaraman, Ashok R ; Spring, David R</creator><creatorcontrib>Alza, Esther ; Laraia, Luca ; Ibbeson, Brett M ; Collins, Súil ; Galloway, Warren R J D ; Stokes, Jamie E ; Venkitaraman, Ashok R ; Spring, David R</creatorcontrib><description>The synthesis of a previously undescribed sp -rich 6-5-5-6 tetracyclic ring scaffold using a palladium catalysed domino Heck-Suzuki reaction is reported. This reaction is high-yielding, selective for the domino process over the direct Suzuki reaction and tolerant towards a variety of boronic acids. The novel scaffold can also be accessed domino Heck-Stille and radical cyclisations. Compounds based around this scaffold were found to be effective antimitotic agents in a human cancer cell line. Detailed phenotypic profiling showed that the compounds affected the congression of chromosomes to give mitotic arrest and apoptotic cell death. Thus, a novel structural class of antimitotic agents that does not disrupt the tubulin network has been identified.</description><identifier>ISSN: 2041-6520</identifier><identifier>EISSN: 2041-6539</identifier><identifier>DOI: 10.1039/c4sc02547d</identifier><identifier>PMID: 28966765</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Chemistry</subject><ispartof>Chemical science (Cambridge), 2015-01, Vol.6 (1), p.390-396</ispartof><rights>This journal is © The Royal Society of Chemistry 2014 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-8703a440308710985251d33829941a2a5df81547ec05f340568445890ef25103</citedby><cites>FETCH-LOGICAL-c378t-8703a440308710985251d33829941a2a5df81547ec05f340568445890ef25103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586250/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5586250/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28966765$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alza, Esther</creatorcontrib><creatorcontrib>Laraia, Luca</creatorcontrib><creatorcontrib>Ibbeson, Brett M</creatorcontrib><creatorcontrib>Collins, Súil</creatorcontrib><creatorcontrib>Galloway, Warren R J D</creatorcontrib><creatorcontrib>Stokes, Jamie E</creatorcontrib><creatorcontrib>Venkitaraman, Ashok R</creatorcontrib><creatorcontrib>Spring, David R</creatorcontrib><title>Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck-Suzuki reaction</title><title>Chemical science (Cambridge)</title><addtitle>Chem Sci</addtitle><description>The synthesis of a previously undescribed sp -rich 6-5-5-6 tetracyclic ring scaffold using a palladium catalysed domino Heck-Suzuki reaction is reported. This reaction is high-yielding, selective for the domino process over the direct Suzuki reaction and tolerant towards a variety of boronic acids. The novel scaffold can also be accessed domino Heck-Stille and radical cyclisations. Compounds based around this scaffold were found to be effective antimitotic agents in a human cancer cell line. Detailed phenotypic profiling showed that the compounds affected the congression of chromosomes to give mitotic arrest and apoptotic cell death. Thus, a novel structural class of antimitotic agents that does not disrupt the tubulin network has been identified.</description><subject>Chemistry</subject><issn>2041-6520</issn><issn>2041-6539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNpVkVtr3DAQhUVJaEKyL_kBRY8l4FZXW34plG0uhUAedt-FIo-zamTJkeQN219f57Y08zID5-PMDAehM0q-UcLb71ZkS5gUTfcJHTMiaFVL3h7sZ0aO0CLnP2QuzqlkzWd0xFRb100tj9G02oWygewyjj02OMQteDxGv7M7653FyYV7nK3p--g7_OTKBptQ3OBKLLM8pjhCKg4y3jozG2TwYIvbAu7i4ELE12AfqtX0d3pwOIGZtRhO0WFvfIbFWz9B68uL9fK6urm9-r38eVNZ3qhSqYZwIwThRDWUtEoySTvOFWtbQQ0zsusVnV8HS2TPBZG1EkKqlkA_k4SfoB-vtuN0N0BnIZRkvB6TG0za6Wic_qgEt9H3caulVDWTzwZf3wxSfJwgFz24bMF7EyBOWdNWyIZxQfmMnr-iNsWcE_T7NZTo56T0UqyWL0n9muEv_x-2R99z4f8AU16PYw</recordid><startdate>20150101</startdate><enddate>20150101</enddate><creator>Alza, Esther</creator><creator>Laraia, Luca</creator><creator>Ibbeson, Brett M</creator><creator>Collins, Súil</creator><creator>Galloway, Warren R J D</creator><creator>Stokes, Jamie E</creator><creator>Venkitaraman, Ashok R</creator><creator>Spring, David R</creator><general>Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150101</creationdate><title>Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck-Suzuki reaction</title><author>Alza, Esther ; Laraia, Luca ; Ibbeson, Brett M ; Collins, Súil ; Galloway, Warren R J D ; Stokes, Jamie E ; Venkitaraman, Ashok R ; Spring, David R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-8703a440308710985251d33829941a2a5df81547ec05f340568445890ef25103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alza, Esther</creatorcontrib><creatorcontrib>Laraia, Luca</creatorcontrib><creatorcontrib>Ibbeson, Brett M</creatorcontrib><creatorcontrib>Collins, Súil</creatorcontrib><creatorcontrib>Galloway, Warren R J D</creatorcontrib><creatorcontrib>Stokes, Jamie E</creatorcontrib><creatorcontrib>Venkitaraman, Ashok R</creatorcontrib><creatorcontrib>Spring, David R</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Chemical science (Cambridge)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alza, Esther</au><au>Laraia, Luca</au><au>Ibbeson, Brett M</au><au>Collins, Súil</au><au>Galloway, Warren R J D</au><au>Stokes, Jamie E</au><au>Venkitaraman, Ashok R</au><au>Spring, David R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck-Suzuki reaction</atitle><jtitle>Chemical science (Cambridge)</jtitle><addtitle>Chem Sci</addtitle><date>2015-01-01</date><risdate>2015</risdate><volume>6</volume><issue>1</issue><spage>390</spage><epage>396</epage><pages>390-396</pages><issn>2041-6520</issn><eissn>2041-6539</eissn><abstract>The synthesis of a previously undescribed sp -rich 6-5-5-6 tetracyclic ring scaffold using a palladium catalysed domino Heck-Suzuki reaction is reported. This reaction is high-yielding, selective for the domino process over the direct Suzuki reaction and tolerant towards a variety of boronic acids. The novel scaffold can also be accessed domino Heck-Stille and radical cyclisations. Compounds based around this scaffold were found to be effective antimitotic agents in a human cancer cell line. Detailed phenotypic profiling showed that the compounds affected the congression of chromosomes to give mitotic arrest and apoptotic cell death. Thus, a novel structural class of antimitotic agents that does not disrupt the tubulin network has been identified.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>28966765</pmid><doi>10.1039/c4sc02547d</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
fulltext	fulltext
identifier	ISSN: 2041-6520
ispartof	Chemical science (Cambridge), 2015-01, Vol.6 (1), p.390-396
issn	2041-6520 2041-6539
language	eng
recordid	cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5586250
source	DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access
subjects	Chemistry
title	Synthesis of a novel polycyclic ring scaffold with antimitotic properties via a selective domino Heck-Suzuki reaction
url	https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-14T00%3A25%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Synthesis%20of%20a%20novel%20polycyclic%20ring%20scaffold%20with%20antimitotic%20properties%20via%20a%20selective%20domino%20Heck-Suzuki%20reaction&rft.jtitle=Chemical%20science%20(Cambridge)&rft.au=Alza,%20Esther&rft.date=2015-01-01&rft.volume=6&rft.issue=1&rft.spage=390&rft.epage=396&rft.pages=390-396&rft.issn=2041-6520&rft.eissn=2041-6539&rft_id=info:doi/10.1039/c4sc02547d&rft_dat=%3Cproquest_pubme%3E1945723413%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1945723413&rft_id=info:pmid/28966765&rfr_iscdi=true