Enantioselective Synthesis of Iclaprim Enantiomers―A Versatile Approach to 2-Substituted Chiral Chromenes
Both enantiomers of the DHFR inhibitor iclaprim (R)-1 and (S)-1 were synthesized from the cyclopropyl homoallyl alcohols (R)-6 and (S)-6, respectively. As key steps these transformations include a Mitsunobu reaction and the formation of the diaminopyrimidine unit prior to a novel cyclization procedu...
Gespeichert in:
| Veröffentlicht in: | Journal of organic chemistry 2010-06, Vol.75 (11), p.3781-3785 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 3785 |
|---|---|
| container_issue | 11 |
| container_start_page | 3781 |
| container_title | Journal of organic chemistry |
| container_volume | 75 |
| creator | Tahtaoui, Chouaib Demailly, Arnold Guidemann, Carole Joyeux, Cécile Schneider, Peter |
| description | Both enantiomers of the DHFR inhibitor iclaprim (R)-1 and (S)-1 were synthesized from the cyclopropyl homoallyl alcohols (R)-6 and (S)-6, respectively. As key steps these transformations include a Mitsunobu reaction and the formation of the diaminopyrimidine unit prior to a novel cyclization procedure to obtain the desired chromene heterocycle. The moderate enantioselectivity of the products (R)-1 and (S)-1 is related to the Mitsunobu reaction, which unfortunately did not proceed with complete inversion of configuration. |
| doi_str_mv | 10.1021/jo100566c |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_733109722</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>733109722</sourcerecordid><originalsourceid>FETCH-LOGICAL-a410t-b6ab8babe8b57d78cd337ada726c73c1848fe80147991a7e55aa18d498392ab33</originalsourceid><addsrcrecordid>eNpt0MtO3DAUBmALtYLhsugLVN5UqIsUX-LYWY5GUJCQWHDZRifOicY0k0x9nErs-hJ9wT4JRkxhU2-OF59_2z9jn6T4JoWSZ4-TFMJUld9jC2mUKKpalB_YQgilCq0qfcAOiR5FXsaYfXagRFlWVtgF-3E-wpjCRDigT-EX8tunMa2RAvGp51d-gG0MG75jG4z09_efJX_IG0hhQL7cbuMEfs3TxFVxO7eUQpoTdny1DhGGPGI-NyIds489DIQnu3nE7i_O71aXxfXN96vV8rqAUopUtBW0roUWXWtsZ53vtLbQgVWVt9pLV7oenZClrWsJFo0BkK4ra6drBa3WR-z0NTc_7OeMlJpNII_DACNOMzVWaylqq1SWX1-ljxNRxL55-SzEp0aK5qXa5q3abD_vUud2g92b_NdlBl92AMjD0EcYfaB3p5xRttTvDjzl_DmOuYz_XPgMydKOrw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>733109722</pqid></control><display><type>article</type><title>Enantioselective Synthesis of Iclaprim Enantiomers―A Versatile Approach to 2-Substituted Chiral Chromenes</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Tahtaoui, Chouaib ; Demailly, Arnold ; Guidemann, Carole ; Joyeux, Cécile ; Schneider, Peter</creator><creatorcontrib>Tahtaoui, Chouaib ; Demailly, Arnold ; Guidemann, Carole ; Joyeux, Cécile ; Schneider, Peter</creatorcontrib><description>Both enantiomers of the DHFR inhibitor iclaprim (R)-1 and (S)-1 were synthesized from the cyclopropyl homoallyl alcohols (R)-6 and (S)-6, respectively. As key steps these transformations include a Mitsunobu reaction and the formation of the diaminopyrimidine unit prior to a novel cyclization procedure to obtain the desired chromene heterocycle. The moderate enantioselectivity of the products (R)-1 and (S)-1 is related to the Mitsunobu reaction, which unfortunately did not proceed with complete inversion of configuration.</description><identifier>ISSN: 0022-3263</identifier><identifier>EISSN: 1520-6904</identifier><identifier>DOI: 10.1021/jo100566c</identifier><identifier>PMID: 20446707</identifier><identifier>CODEN: JOCEAH</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Alcohols - chemistry ; Alicyclic compounds ; Alicyclic compounds, terpenoids, prostaglandins, steroids ; Benzopyrans - chemical synthesis ; Chemistry ; Exact sciences and technology ; Folic Acid Antagonists - chemical synthesis ; Heterocyclic compounds ; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives ; Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings ; Organic chemistry ; Preparations and properties ; Pyrimidines - chemical synthesis ; Stereoisomerism ; Tetrahydrofolate Dehydrogenase</subject><ispartof>Journal of organic chemistry, 2010-06, Vol.75 (11), p.3781-3785</ispartof><rights>Copyright © 2010 American Chemical Society</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a410t-b6ab8babe8b57d78cd337ada726c73c1848fe80147991a7e55aa18d498392ab33</citedby><cites>FETCH-LOGICAL-a410t-b6ab8babe8b57d78cd337ada726c73c1848fe80147991a7e55aa18d498392ab33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jo100566c$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jo100566c$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22852743$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20446707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tahtaoui, Chouaib</creatorcontrib><creatorcontrib>Demailly, Arnold</creatorcontrib><creatorcontrib>Guidemann, Carole</creatorcontrib><creatorcontrib>Joyeux, Cécile</creatorcontrib><creatorcontrib>Schneider, Peter</creatorcontrib><title>Enantioselective Synthesis of Iclaprim Enantiomers―A Versatile Approach to 2-Substituted Chiral Chromenes</title><title>Journal of organic chemistry</title><addtitle>J. Org. Chem</addtitle><description>Both enantiomers of the DHFR inhibitor iclaprim (R)-1 and (S)-1 were synthesized from the cyclopropyl homoallyl alcohols (R)-6 and (S)-6, respectively. As key steps these transformations include a Mitsunobu reaction and the formation of the diaminopyrimidine unit prior to a novel cyclization procedure to obtain the desired chromene heterocycle. The moderate enantioselectivity of the products (R)-1 and (S)-1 is related to the Mitsunobu reaction, which unfortunately did not proceed with complete inversion of configuration.</description><subject>Alcohols - chemistry</subject><subject>Alicyclic compounds</subject><subject>Alicyclic compounds, terpenoids, prostaglandins, steroids</subject><subject>Benzopyrans - chemical synthesis</subject><subject>Chemistry</subject><subject>Exact sciences and technology</subject><subject>Folic Acid Antagonists - chemical synthesis</subject><subject>Heterocyclic compounds</subject><subject>Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives</subject><subject>Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings</subject><subject>Organic chemistry</subject><subject>Preparations and properties</subject><subject>Pyrimidines - chemical synthesis</subject><subject>Stereoisomerism</subject><subject>Tetrahydrofolate Dehydrogenase</subject><issn>0022-3263</issn><issn>1520-6904</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0MtO3DAUBmALtYLhsugLVN5UqIsUX-LYWY5GUJCQWHDZRifOicY0k0x9nErs-hJ9wT4JRkxhU2-OF59_2z9jn6T4JoWSZ4-TFMJUld9jC2mUKKpalB_YQgilCq0qfcAOiR5FXsaYfXagRFlWVtgF-3E-wpjCRDigT-EX8tunMa2RAvGp51d-gG0MG75jG4z09_efJX_IG0hhQL7cbuMEfs3TxFVxO7eUQpoTdny1DhGGPGI-NyIds489DIQnu3nE7i_O71aXxfXN96vV8rqAUopUtBW0roUWXWtsZ53vtLbQgVWVt9pLV7oenZClrWsJFo0BkK4ra6drBa3WR-z0NTc_7OeMlJpNII_DACNOMzVWaylqq1SWX1-ljxNRxL55-SzEp0aK5qXa5q3abD_vUud2g92b_NdlBl92AMjD0EcYfaB3p5xRttTvDjzl_DmOuYz_XPgMydKOrw</recordid><startdate>20100604</startdate><enddate>20100604</enddate><creator>Tahtaoui, Chouaib</creator><creator>Demailly, Arnold</creator><creator>Guidemann, Carole</creator><creator>Joyeux, Cécile</creator><creator>Schneider, Peter</creator><general>American Chemical Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20100604</creationdate><title>Enantioselective Synthesis of Iclaprim Enantiomers―A Versatile Approach to 2-Substituted Chiral Chromenes</title><author>Tahtaoui, Chouaib ; Demailly, Arnold ; Guidemann, Carole ; Joyeux, Cécile ; Schneider, Peter</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a410t-b6ab8babe8b57d78cd337ada726c73c1848fe80147991a7e55aa18d498392ab33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Alcohols - chemistry</topic><topic>Alicyclic compounds</topic><topic>Alicyclic compounds, terpenoids, prostaglandins, steroids</topic><topic>Benzopyrans - chemical synthesis</topic><topic>Chemistry</topic><topic>Exact sciences and technology</topic><topic>Folic Acid Antagonists - chemical synthesis</topic><topic>Heterocyclic compounds</topic><topic>Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives</topic><topic>Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings</topic><topic>Organic chemistry</topic><topic>Preparations and properties</topic><topic>Pyrimidines - chemical synthesis</topic><topic>Stereoisomerism</topic><topic>Tetrahydrofolate Dehydrogenase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tahtaoui, Chouaib</creatorcontrib><creatorcontrib>Demailly, Arnold</creatorcontrib><creatorcontrib>Guidemann, Carole</creatorcontrib><creatorcontrib>Joyeux, Cécile</creatorcontrib><creatorcontrib>Schneider, Peter</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of organic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tahtaoui, Chouaib</au><au>Demailly, Arnold</au><au>Guidemann, Carole</au><au>Joyeux, Cécile</au><au>Schneider, Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Enantioselective Synthesis of Iclaprim Enantiomers―A Versatile Approach to 2-Substituted Chiral Chromenes</atitle><jtitle>Journal of organic chemistry</jtitle><addtitle>J. Org. Chem</addtitle><date>2010-06-04</date><risdate>2010</risdate><volume>75</volume><issue>11</issue><spage>3781</spage><epage>3785</epage><pages>3781-3785</pages><issn>0022-3263</issn><eissn>1520-6904</eissn><coden>JOCEAH</coden><abstract>Both enantiomers of the DHFR inhibitor iclaprim (R)-1 and (S)-1 were synthesized from the cyclopropyl homoallyl alcohols (R)-6 and (S)-6, respectively. As key steps these transformations include a Mitsunobu reaction and the formation of the diaminopyrimidine unit prior to a novel cyclization procedure to obtain the desired chromene heterocycle. The moderate enantioselectivity of the products (R)-1 and (S)-1 is related to the Mitsunobu reaction, which unfortunately did not proceed with complete inversion of configuration.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>20446707</pmid><doi>10.1021/jo100566c</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-3263 |
| ispartof | Journal of organic chemistry, 2010-06, Vol.75 (11), p.3781-3785 |
| issn | 0022-3263 1520-6904 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_733109722 |
| source | MEDLINE; American Chemical Society Journals |
| subjects | Alcohols - chemistry Alicyclic compounds Alicyclic compounds, terpenoids, prostaglandins, steroids Benzopyrans - chemical synthesis Chemistry Exact sciences and technology Folic Acid Antagonists - chemical synthesis Heterocyclic compounds Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings Organic chemistry Preparations and properties Pyrimidines - chemical synthesis Stereoisomerism Tetrahydrofolate Dehydrogenase |
| title | Enantioselective Synthesis of Iclaprim Enantiomers―A Versatile Approach to 2-Substituted Chiral Chromenes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T10%3A31%3A46IST&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=Enantioselective%20Synthesis%20of%20Iclaprim%20Enantiomers%E2%80%95A%20Versatile%20Approach%20to%202-Substituted%20Chiral%20Chromenes&rft.jtitle=Journal%20of%20organic%20chemistry&rft.au=Tahtaoui,%20Chouaib&rft.date=2010-06-04&rft.volume=75&rft.issue=11&rft.spage=3781&rft.epage=3785&rft.pages=3781-3785&rft.issn=0022-3263&rft.eissn=1520-6904&rft.coden=JOCEAH&rft_id=info:doi/10.1021/jo100566c&rft_dat=%3Cproquest_cross%3E733109722%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=733109722&rft_id=info:pmid/20446707&rfr_iscdi=true |