Oxalyl Boronates Enable Modular Synthesis of Bioactive Imidazoles

Described herein is the preparation of oxalyl boronate building blocks and their application for the construction of heterocycles. The oxalyl unit, readily accessible through commercially available starting materials, enables a modular approach for the synthesis of imidazoles. A variety of aromatic,...

Full description

Saved in:
Bibliographic Details
Published in:Angewandte Chemie International Edition 2017-05, Vol.56 (22), p.6264-6267
Main Authors: Lee, C. Frank, Holownia, Aleksandra, Bennett, James M., Elkins, Jonathan M., St. Denis, Jeffrey D., Adachi, Shinya, Yudin, Andrei K.
Format: Article
Language:English
Subjects:
Accessibility
Biocompatibility
biological activity
Biomedical materials
boron
Construction
Cross coupling
heterocycles
Imidazole
Inhibitors
Kinases
Palladium
Protein kinase
Scaffolds
Surgical implants
Synthesis
synthetic methods
Threonine
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by cdi_FETCH-LOGICAL-c5166-2986846f15a34915b0b473a16ca3bd2003e3b9f4af7f8cc9cdac25c263ce6d753
cites cdi_FETCH-LOGICAL-c5166-2986846f15a34915b0b473a16ca3bd2003e3b9f4af7f8cc9cdac25c263ce6d753
container_end_page 6267
container_issue 22
container_start_page 6264
container_title Angewandte Chemie International Edition
container_volume 56
creator Lee, C. Frank
Holownia, Aleksandra
Bennett, James M.
Elkins, Jonathan M.
St. Denis, Jeffrey D.
Adachi, Shinya
Yudin, Andrei K.
description Described herein is the preparation of oxalyl boronate building blocks and their application for the construction of heterocycles. The oxalyl unit, readily accessible through commercially available starting materials, enables a modular approach for the synthesis of imidazoles. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium‐catalyzed cross‐coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine‐protein kinase STK10 were synthesized. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium‐catalyzed cross‐coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine‐protein kinase STK10 were synthesized.
doi_str_mv 10.1002/anie.201611006
format article
fullrecord <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1875143058</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1899036334</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5166-2986846f15a34915b0b473a16ca3bd2003e3b9f4af7f8cc9cdac25c263ce6d753</originalsourceid><addsrcrecordid>eNqF0M1LwzAYBvAgipsfV49S8OKlMx9Nmhy3MXUw3UE9lzRNMSNtZtOq9a83Y3OCF095A788vHkAuEBwhCDEN7I2eoQhYihc2QEYIopRTNKUHIY5ISROOUUDcOL9KnjOITsGA8wxSzETQzBefkrb22jiGlfLVvtoVsvc6ujBFZ2VTfTU1-2r9sZHrowmxknVmncdzStTyC9ntT8DR6W0Xp_vzlPwcjt7nt7Hi-XdfDpexIoixmIsOOMJKxGVJBGI5jBPUiIRU5LkBYaQaJKLMpFlWnKlhCqkwlRhRpRmRUrJKbje5q4b99Zp32aV8UpbK2vtOp8hntLwYUh5oFd_6Mp1TR22C0oISBghSVCjrVKN877RZbZuTCWbPkMw25SbbcrN9uWGB5e72C6vdLHnP20GILbgw1jd_xOXjR_ns9_wb_QyhJI</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1899036334</pqid></control><display><type>article</type><title>Oxalyl Boronates Enable Modular Synthesis of Bioactive Imidazoles</title><source>Wiley-Blackwell Read &amp; Publish Collection</source><creator>Lee, C. Frank ; Holownia, Aleksandra ; Bennett, James M. ; Elkins, Jonathan M. ; St. Denis, Jeffrey D. ; Adachi, Shinya ; Yudin, Andrei K.</creator><creatorcontrib>Lee, C. Frank ; Holownia, Aleksandra ; Bennett, James M. ; Elkins, Jonathan M. ; St. Denis, Jeffrey D. ; Adachi, Shinya ; Yudin, Andrei K.</creatorcontrib><description>Described herein is the preparation of oxalyl boronate building blocks and their application for the construction of heterocycles. The oxalyl unit, readily accessible through commercially available starting materials, enables a modular approach for the synthesis of imidazoles. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium‐catalyzed cross‐coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine‐protein kinase STK10 were synthesized. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium‐catalyzed cross‐coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine‐protein kinase STK10 were synthesized.</description><edition>International ed. in English</edition><identifier>ISSN: 1433-7851</identifier><identifier>EISSN: 1521-3773</identifier><identifier>DOI: 10.1002/anie.201611006</identifier><identifier>PMID: 28267269</identifier><language>eng</language><publisher>Germany: Wiley Subscription Services, Inc</publisher><subject>Accessibility ; Biocompatibility ; biological activity ; Biomedical materials ; boron ; Construction ; Cross coupling ; heterocycles ; Imidazole ; Inhibitors ; Kinases ; Palladium ; Protein kinase ; Scaffolds ; Surgical implants ; Synthesis ; synthetic methods ; Threonine</subject><ispartof>Angewandte Chemie International Edition, 2017-05, Vol.56 (22), p.6264-6267</ispartof><rights>2017 Wiley‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim</rights><rights>2017 Wiley-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5166-2986846f15a34915b0b473a16ca3bd2003e3b9f4af7f8cc9cdac25c263ce6d753</citedby><cites>FETCH-LOGICAL-c5166-2986846f15a34915b0b473a16ca3bd2003e3b9f4af7f8cc9cdac25c263ce6d753</cites><orcidid>0000-0003-3170-9103</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28267269$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, C. Frank</creatorcontrib><creatorcontrib>Holownia, Aleksandra</creatorcontrib><creatorcontrib>Bennett, James M.</creatorcontrib><creatorcontrib>Elkins, Jonathan M.</creatorcontrib><creatorcontrib>St. Denis, Jeffrey D.</creatorcontrib><creatorcontrib>Adachi, Shinya</creatorcontrib><creatorcontrib>Yudin, Andrei K.</creatorcontrib><title>Oxalyl Boronates Enable Modular Synthesis of Bioactive Imidazoles</title><title>Angewandte Chemie International Edition</title><addtitle>Angew Chem Int Ed Engl</addtitle><description>Described herein is the preparation of oxalyl boronate building blocks and their application for the construction of heterocycles. The oxalyl unit, readily accessible through commercially available starting materials, enables a modular approach for the synthesis of imidazoles. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium‐catalyzed cross‐coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine‐protein kinase STK10 were synthesized. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium‐catalyzed cross‐coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine‐protein kinase STK10 were synthesized.</description><subject>Accessibility</subject><subject>Biocompatibility</subject><subject>biological activity</subject><subject>Biomedical materials</subject><subject>boron</subject><subject>Construction</subject><subject>Cross coupling</subject><subject>heterocycles</subject><subject>Imidazole</subject><subject>Inhibitors</subject><subject>Kinases</subject><subject>Palladium</subject><subject>Protein kinase</subject><subject>Scaffolds</subject><subject>Surgical implants</subject><subject>Synthesis</subject><subject>synthetic methods</subject><subject>Threonine</subject><issn>1433-7851</issn><issn>1521-3773</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><recordid>eNqF0M1LwzAYBvAgipsfV49S8OKlMx9Nmhy3MXUw3UE9lzRNMSNtZtOq9a83Y3OCF095A788vHkAuEBwhCDEN7I2eoQhYihc2QEYIopRTNKUHIY5ISROOUUDcOL9KnjOITsGA8wxSzETQzBefkrb22jiGlfLVvtoVsvc6ujBFZ2VTfTU1-2r9sZHrowmxknVmncdzStTyC9ntT8DR6W0Xp_vzlPwcjt7nt7Hi-XdfDpexIoixmIsOOMJKxGVJBGI5jBPUiIRU5LkBYaQaJKLMpFlWnKlhCqkwlRhRpRmRUrJKbje5q4b99Zp32aV8UpbK2vtOp8hntLwYUh5oFd_6Mp1TR22C0oISBghSVCjrVKN877RZbZuTCWbPkMw25SbbcrN9uWGB5e72C6vdLHnP20GILbgw1jd_xOXjR_ns9_wb_QyhJI</recordid><startdate>20170522</startdate><enddate>20170522</enddate><creator>Lee, C. Frank</creator><creator>Holownia, Aleksandra</creator><creator>Bennett, James M.</creator><creator>Elkins, Jonathan M.</creator><creator>St. Denis, Jeffrey D.</creator><creator>Adachi, Shinya</creator><creator>Yudin, Andrei K.</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-3170-9103</orcidid></search><sort><creationdate>20170522</creationdate><title>Oxalyl Boronates Enable Modular Synthesis of Bioactive Imidazoles</title><author>Lee, C. Frank ; Holownia, Aleksandra ; Bennett, James M. ; Elkins, Jonathan M. ; St. Denis, Jeffrey D. ; Adachi, Shinya ; Yudin, Andrei K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5166-2986846f15a34915b0b473a16ca3bd2003e3b9f4af7f8cc9cdac25c263ce6d753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Accessibility</topic><topic>Biocompatibility</topic><topic>biological activity</topic><topic>Biomedical materials</topic><topic>boron</topic><topic>Construction</topic><topic>Cross coupling</topic><topic>heterocycles</topic><topic>Imidazole</topic><topic>Inhibitors</topic><topic>Kinases</topic><topic>Palladium</topic><topic>Protein kinase</topic><topic>Scaffolds</topic><topic>Surgical implants</topic><topic>Synthesis</topic><topic>synthetic methods</topic><topic>Threonine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, C. Frank</creatorcontrib><creatorcontrib>Holownia, Aleksandra</creatorcontrib><creatorcontrib>Bennett, James M.</creatorcontrib><creatorcontrib>Elkins, Jonathan M.</creatorcontrib><creatorcontrib>St. Denis, Jeffrey D.</creatorcontrib><creatorcontrib>Adachi, Shinya</creatorcontrib><creatorcontrib>Yudin, Andrei K.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>ProQuest Health &amp; 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>Lee, C. Frank</au><au>Holownia, Aleksandra</au><au>Bennett, James M.</au><au>Elkins, Jonathan M.</au><au>St. Denis, Jeffrey D.</au><au>Adachi, Shinya</au><au>Yudin, Andrei K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Oxalyl Boronates Enable Modular Synthesis of Bioactive Imidazoles</atitle><jtitle>Angewandte Chemie International Edition</jtitle><addtitle>Angew Chem Int Ed Engl</addtitle><date>2017-05-22</date><risdate>2017</risdate><volume>56</volume><issue>22</issue><spage>6264</spage><epage>6267</epage><pages>6264-6267</pages><issn>1433-7851</issn><eissn>1521-3773</eissn><abstract>Described herein is the preparation of oxalyl boronate building blocks and their application for the construction of heterocycles. The oxalyl unit, readily accessible through commercially available starting materials, enables a modular approach for the synthesis of imidazoles. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium‐catalyzed cross‐coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine‐protein kinase STK10 were synthesized. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium‐catalyzed cross‐coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine‐protein kinase STK10 were synthesized.</abstract><cop>Germany</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28267269</pmid><doi>10.1002/anie.201611006</doi><tpages>4</tpages><edition>International ed. in English</edition><orcidid>https://orcid.org/0000-0003-3170-9103</orcidid><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1433-7851
ispartof Angewandte Chemie International Edition, 2017-05, Vol.56 (22), p.6264-6267
issn 1433-7851
1521-3773
language eng
recordid cdi_proquest_miscellaneous_1875143058
source Wiley-Blackwell Read & Publish Collection
subjects Accessibility
Biocompatibility
biological activity
Biomedical materials
boron
Construction
Cross coupling
heterocycles
Imidazole
Inhibitors
Kinases
Palladium
Protein kinase
Scaffolds
Surgical implants
Synthesis
synthetic methods
Threonine
title Oxalyl Boronates Enable Modular Synthesis of Bioactive Imidazoles
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-28T06%3A31%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Oxalyl%20Boronates%20Enable%20Modular%20Synthesis%20of%20Bioactive%20Imidazoles&rft.jtitle=Angewandte%20Chemie%20International%20Edition&rft.au=Lee,%20C.%20Frank&rft.date=2017-05-22&rft.volume=56&rft.issue=22&rft.spage=6264&rft.epage=6267&rft.pages=6264-6267&rft.issn=1433-7851&rft.eissn=1521-3773&rft_id=info:doi/10.1002/anie.201611006&rft_dat=%3Cproquest_cross%3E1899036334%3C/proquest_cross%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c5166-2986846f15a34915b0b473a16ca3bd2003e3b9f4af7f8cc9cdac25c263ce6d753%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1899036334&rft_id=info:pmid/28267269&rfr_iscdi=true