Parallel Synthesis of Novel Heteroaromatic Acromelic Acid Analogues from Kainic Acid
A range of new C-4 heteroaromatic acromelic acid analogues has been synthesized in a parallel fashion from (−)-α-kainic acid 1. Protection of the amine and carboxylate groups of 1 followed by ozonolysis gave methyl ketone 8. A silyl enol ether 9, generated regiospecifically from the methyl ketone 8...
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| Veröffentlicht in: | Journal of organic chemistry 2001-04, Vol.66 (8), p.2588-2596 |
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| container_end_page | 2596 |
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| container_issue | 8 |
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| container_title | Journal of organic chemistry |
| container_volume | 66 |
| creator | Baldwin, Jack E Fryer, Andrew M Pritchard, Gareth J |
| description | A range of new C-4 heteroaromatic acromelic acid analogues has been synthesized in a parallel fashion from (−)-α-kainic acid 1. Protection of the amine and carboxylate groups of 1 followed by ozonolysis gave methyl ketone 8. A silyl enol ether 9, generated regiospecifically from the methyl ketone 8 using “kinetic” conditions, was brominated in situ with phenyltrimethylammonium perbromide to give the key α-bromo ketone 10. Parallel cyclization reactions of bromo ketone 10 with thioamides and thioureas were then performed. The aromatic heterocyclic derivatives 11a−d and 19 produced were deprotected to give the new kainoid amino acids 6a−d and 25 in excellent yield. Compounds 6a and 6c show strong binding to the kainate receptor. Reaction of 10 with alternative condensing agents was also briefly investigated. |
| doi_str_mv | 10.1021/jo000846l |
| format | Article |
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Protection of the amine and carboxylate groups of 1 followed by ozonolysis gave methyl ketone 8. A silyl enol ether 9, generated regiospecifically from the methyl ketone 8 using “kinetic” conditions, was brominated in situ with phenyltrimethylammonium perbromide to give the key α-bromo ketone 10. Parallel cyclization reactions of bromo ketone 10 with thioamides and thioureas were then performed. The aromatic heterocyclic derivatives 11a−d and 19 produced were deprotected to give the new kainoid amino acids 6a−d and 25 in excellent yield. Compounds 6a and 6c show strong binding to the kainate receptor. Reaction of 10 with alternative condensing agents was also briefly investigated.</description><identifier>ISSN: 0022-3263</identifier><identifier>EISSN: 1520-6904</identifier><identifier>DOI: 10.1021/jo000846l</identifier><identifier>PMID: 11304175</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Animals ; Anthelmintics - chemical synthesis ; Excitatory Amino Acid Agonists - chemical synthesis ; Excitatory Amino Acid Antagonists - chemical synthesis ; Heterocyclic Compounds - chemical synthesis ; Humans ; Insecticides - chemical synthesis ; Kainic Acid - analogs & derivatives ; Kainic Acid - chemical synthesis</subject><ispartof>Journal of organic chemistry, 2001-04, Vol.66 (8), p.2588-2596</ispartof><rights>Copyright © 2001 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a374t-3b503f046239223802ad068535c089d5f29d0395e4718a8227ffc2e80e31cd9a3</citedby><cites>FETCH-LOGICAL-a374t-3b503f046239223802ad068535c089d5f29d0395e4718a8227ffc2e80e31cd9a3</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/jo000846l$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jo000846l$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11304175$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Baldwin, Jack E</creatorcontrib><creatorcontrib>Fryer, Andrew M</creatorcontrib><creatorcontrib>Pritchard, Gareth J</creatorcontrib><title>Parallel Synthesis of Novel Heteroaromatic Acromelic Acid Analogues from Kainic Acid</title><title>Journal of organic chemistry</title><addtitle>J. Org. Chem</addtitle><description>A range of new C-4 heteroaromatic acromelic acid analogues has been synthesized in a parallel fashion from (−)-α-kainic acid 1. Protection of the amine and carboxylate groups of 1 followed by ozonolysis gave methyl ketone 8. A silyl enol ether 9, generated regiospecifically from the methyl ketone 8 using “kinetic” conditions, was brominated in situ with phenyltrimethylammonium perbromide to give the key α-bromo ketone 10. Parallel cyclization reactions of bromo ketone 10 with thioamides and thioureas were then performed. The aromatic heterocyclic derivatives 11a−d and 19 produced were deprotected to give the new kainoid amino acids 6a−d and 25 in excellent yield. Compounds 6a and 6c show strong binding to the kainate receptor. Reaction of 10 with alternative condensing agents was also briefly investigated.</description><subject>Animals</subject><subject>Anthelmintics - chemical synthesis</subject><subject>Excitatory Amino Acid Agonists - chemical synthesis</subject><subject>Excitatory Amino Acid Antagonists - chemical synthesis</subject><subject>Heterocyclic Compounds - chemical synthesis</subject><subject>Humans</subject><subject>Insecticides - chemical synthesis</subject><subject>Kainic Acid - analogs & derivatives</subject><subject>Kainic Acid - chemical synthesis</subject><issn>0022-3263</issn><issn>1520-6904</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkEFPAjEQhRujEUQP_gHTiwcPq9N2u9seCRExECUBL16astvqYmFJuxj591aX4MXTvLz3ZWbyELokcEuAkrtlDQAizdwR6hJOIckkpMeoC0BpwmjGOugshGWEgHN-ijqEMEhJzrtoPtVeO2ccnu3WzbsJVcC1xU_1Z7RGpjG-1r5e6aYqcL-IyrhfVZW4v9auftuagG308VhX6310jk6sdsFc7GcPvQzv54NRMnl-eBz0J4lmedokbMGBWUgzyiSlTADVJWSCM16AkCW3VJbAJDdpToQWlObWFtQIMIwUpdSsh27avfGxELyxauOrlfY7RUD9NKMOzUT2qmU328XKlH_kvooIJC1QhcZ8HXLtP1SWs5yr-XSmXtmQSBiO1SDy1y2vixDvbH2sI_xz-BtB_3fF</recordid><startdate>20010420</startdate><enddate>20010420</enddate><creator>Baldwin, Jack E</creator><creator>Fryer, Andrew M</creator><creator>Pritchard, Gareth J</creator><general>American Chemical Society</general><scope>BSCLL</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></search><sort><creationdate>20010420</creationdate><title>Parallel Synthesis of Novel Heteroaromatic Acromelic Acid Analogues from Kainic Acid</title><author>Baldwin, Jack E ; Fryer, Andrew M ; Pritchard, Gareth J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a374t-3b503f046239223802ad068535c089d5f29d0395e4718a8227ffc2e80e31cd9a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Animals</topic><topic>Anthelmintics - chemical synthesis</topic><topic>Excitatory Amino Acid Agonists - chemical synthesis</topic><topic>Excitatory Amino Acid Antagonists - chemical synthesis</topic><topic>Heterocyclic Compounds - chemical synthesis</topic><topic>Humans</topic><topic>Insecticides - chemical synthesis</topic><topic>Kainic Acid - analogs & derivatives</topic><topic>Kainic Acid - chemical synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Baldwin, Jack E</creatorcontrib><creatorcontrib>Fryer, Andrew M</creatorcontrib><creatorcontrib>Pritchard, Gareth J</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Journal of organic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Baldwin, Jack E</au><au>Fryer, Andrew M</au><au>Pritchard, Gareth J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Parallel Synthesis of Novel Heteroaromatic Acromelic Acid Analogues from Kainic Acid</atitle><jtitle>Journal of organic chemistry</jtitle><addtitle>J. Org. Chem</addtitle><date>2001-04-20</date><risdate>2001</risdate><volume>66</volume><issue>8</issue><spage>2588</spage><epage>2596</epage><pages>2588-2596</pages><issn>0022-3263</issn><eissn>1520-6904</eissn><abstract>A range of new C-4 heteroaromatic acromelic acid analogues has been synthesized in a parallel fashion from (−)-α-kainic acid 1. Protection of the amine and carboxylate groups of 1 followed by ozonolysis gave methyl ketone 8. A silyl enol ether 9, generated regiospecifically from the methyl ketone 8 using “kinetic” conditions, was brominated in situ with phenyltrimethylammonium perbromide to give the key α-bromo ketone 10. Parallel cyclization reactions of bromo ketone 10 with thioamides and thioureas were then performed. The aromatic heterocyclic derivatives 11a−d and 19 produced were deprotected to give the new kainoid amino acids 6a−d and 25 in excellent yield. Compounds 6a and 6c show strong binding to the kainate receptor. Reaction of 10 with alternative condensing agents was also briefly investigated.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>11304175</pmid><doi>10.1021/jo000846l</doi><tpages>9</tpages></addata></record> |
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| ispartof | Journal of organic chemistry, 2001-04, Vol.66 (8), p.2588-2596 |
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| source | MEDLINE; American Chemical Society Journals |
| subjects | Animals Anthelmintics - chemical synthesis Excitatory Amino Acid Agonists - chemical synthesis Excitatory Amino Acid Antagonists - chemical synthesis Heterocyclic Compounds - chemical synthesis Humans Insecticides - chemical synthesis Kainic Acid - analogs & derivatives Kainic Acid - chemical synthesis |
| title | Parallel Synthesis of Novel Heteroaromatic Acromelic Acid Analogues from Kainic Acid |
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