Total Synthesis of (+)-Azaspiracid-1. An Exhibition of the Intricacies of Complex Molecule Synthesis
The synthesis of the marine neurotoxin azaspiracid-1 has been accomplished. The individual fragments were synthesized by catalytic enantioselective processes: A hetero-Diels−Alder reaction to afford the E- and HI-ring fragments, a carbonyl-ene reaction to furnish the CD-ring fragment, and a Mukaiyam...
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| Veröffentlicht in: | Journal of the American Chemical Society 2008-12, Vol.130 (48), p.16295-16309 |
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| container_issue | 48 |
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| container_title | Journal of the American Chemical Society |
| container_volume | 130 |
| creator | Evans, David A Kværnø, Lisbet Dunn, Travis B Beauchemin, André Raymer, Brian Mulder, Jason A Olhava, Edward J Juhl, Martin Kagechika, Katsuji Favor, David A |
| description | The synthesis of the marine neurotoxin azaspiracid-1 has been accomplished. The individual fragments were synthesized by catalytic enantioselective processes: A hetero-Diels−Alder reaction to afford the E- and HI-ring fragments, a carbonyl-ene reaction to furnish the CD-ring fragment, and a Mukaiyama aldol reaction to deliver the FG-ring fragment. The subsequent fragment couplings were accomplished by aldol and sulfone anion methodologies. All ketalization events to form the nonacyclic target were accomplished under equilibrating conditions utilizing the imbedded configurations of the molecule to adopt one favored conformation. A final fragment coupling of the anomeric EFGHI-sulfone anion to the ABCD-aldehyde completed the convergent synthesis of (+)-azaspiracid-1. |
| doi_str_mv | 10.1021/ja804659n |
| format | Article |
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All ketalization events to form the nonacyclic target were accomplished under equilibrating conditions utilizing the imbedded configurations of the molecule to adopt one favored conformation. 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An Exhibition of the Intricacies of Complex Molecule Synthesis</title><title>Journal of the American Chemical Society</title><addtitle>J. Am. Chem. Soc</addtitle><description>The synthesis of the marine neurotoxin azaspiracid-1 has been accomplished. The individual fragments were synthesized by catalytic enantioselective processes: A hetero-Diels−Alder reaction to afford the E- and HI-ring fragments, a carbonyl-ene reaction to furnish the CD-ring fragment, and a Mukaiyama aldol reaction to deliver the FG-ring fragment. The subsequent fragment couplings were accomplished by aldol and sulfone anion methodologies. All ketalization events to form the nonacyclic target were accomplished under equilibrating conditions utilizing the imbedded configurations of the molecule to adopt one favored conformation. A final fragment coupling of the anomeric EFGHI-sulfone anion to the ABCD-aldehyde completed the convergent synthesis of (+)-azaspiracid-1.</description><subject>Aldehydes - chemistry</subject><subject>Anions - chemistry</subject><subject>Carbon - chemistry</subject><subject>Catalysis</subject><subject>Chelating Agents - chemistry</subject><subject>Iodine Compounds - chemical synthesis</subject><subject>Iodine Compounds - chemistry</subject><subject>Magnetic Resonance Spectroscopy</subject><subject>Marine Toxins - chemical synthesis</subject><subject>Marine Toxins - chemistry</subject><subject>Methylation</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>Spiro Compounds - chemical synthesis</subject><subject>Spiro Compounds - chemistry</subject><subject>Stereoisomerism</subject><subject>Sulfones - chemistry</subject><subject>Vinyl Compounds - chemistry</subject><issn>0002-7863</issn><issn>1520-5126</issn><issn>1520-5126</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkU1PGzEQhi1UBClw6B-o9tKqCC0dr792L5XSlC8J1EqEHnqxnN1Z4rBZp_ZuFfrr6zRRAImTZc3jZ2b8EvKOwimFjH6emRy4FEW7QwZUZJAKmsk3ZAAAWapyyfbJ2xBm8cqznO6RfVoASFbQAanGrjNNcvvYdlMMNiSuTj6dHKfDvyYsrDelrVJ6mgzb5Gw5tRPbWdeumEgnV23nbRkR_P9s5OaLBpfJjWuw7Bt8kh6S3do0AY825wG5Oz8bjy7T6-8XV6PhdWoEqC6lNWWoIOdQM6W4MiApMlVjmYk6LyaVqSosFIccK1MXDJSAPBPcrLbhFbAD8mXtXfSTOVYlxgFNoxfezo1_1M5Y_bLS2qm-d380i84cRBR83Ai8-91j6PTchhKbxrTo-qCllAWnwCN4vAZL70LwWG-bUNCrTPQ2k8i-fz7VE7kJIQLpGrChw-W2bvyDloopocc_bvXPr-fAvvEb_SvyH9a8KYOeud638VNfafwPO5-iHQ</recordid><startdate>20081203</startdate><enddate>20081203</enddate><creator>Evans, David A</creator><creator>Kværnø, Lisbet</creator><creator>Dunn, Travis B</creator><creator>Beauchemin, André</creator><creator>Raymer, Brian</creator><creator>Mulder, Jason A</creator><creator>Olhava, Edward J</creator><creator>Juhl, Martin</creator><creator>Kagechika, Katsuji</creator><creator>Favor, David A</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><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20081203</creationdate><title>Total Synthesis of (+)-Azaspiracid-1. An Exhibition of the Intricacies of Complex Molecule Synthesis</title><author>Evans, David A ; Kværnø, Lisbet ; Dunn, Travis B ; Beauchemin, André ; Raymer, Brian ; Mulder, Jason A ; Olhava, Edward J ; Juhl, Martin ; Kagechika, Katsuji ; Favor, David A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a507t-1f13e70840f37747a061e37fec25f89bdadde97408edaf9307508254a90064d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Aldehydes - chemistry</topic><topic>Anions - chemistry</topic><topic>Carbon - chemistry</topic><topic>Catalysis</topic><topic>Chelating Agents - chemistry</topic><topic>Iodine Compounds - chemical synthesis</topic><topic>Iodine Compounds - chemistry</topic><topic>Magnetic Resonance Spectroscopy</topic><topic>Marine Toxins - chemical synthesis</topic><topic>Marine Toxins - chemistry</topic><topic>Methylation</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>Spiro Compounds - chemical synthesis</topic><topic>Spiro Compounds - chemistry</topic><topic>Stereoisomerism</topic><topic>Sulfones - chemistry</topic><topic>Vinyl Compounds - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Evans, David A</creatorcontrib><creatorcontrib>Kværnø, Lisbet</creatorcontrib><creatorcontrib>Dunn, Travis B</creatorcontrib><creatorcontrib>Beauchemin, André</creatorcontrib><creatorcontrib>Raymer, Brian</creatorcontrib><creatorcontrib>Mulder, Jason A</creatorcontrib><creatorcontrib>Olhava, Edward J</creatorcontrib><creatorcontrib>Juhl, Martin</creatorcontrib><creatorcontrib>Kagechika, Katsuji</creatorcontrib><creatorcontrib>Favor, David A</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><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of the American Chemical Society</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Evans, David A</au><au>Kværnø, Lisbet</au><au>Dunn, Travis B</au><au>Beauchemin, André</au><au>Raymer, Brian</au><au>Mulder, Jason A</au><au>Olhava, Edward J</au><au>Juhl, Martin</au><au>Kagechika, Katsuji</au><au>Favor, David A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Total Synthesis of (+)-Azaspiracid-1. 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All ketalization events to form the nonacyclic target were accomplished under equilibrating conditions utilizing the imbedded configurations of the molecule to adopt one favored conformation. A final fragment coupling of the anomeric EFGHI-sulfone anion to the ABCD-aldehyde completed the convergent synthesis of (+)-azaspiracid-1.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>19006391</pmid><doi>10.1021/ja804659n</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| language | eng |
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| source | ACS Publications; MEDLINE |
| subjects | Aldehydes - chemistry Anions - chemistry Carbon - chemistry Catalysis Chelating Agents - chemistry Iodine Compounds - chemical synthesis Iodine Compounds - chemistry Magnetic Resonance Spectroscopy Marine Toxins - chemical synthesis Marine Toxins - chemistry Methylation Models, Molecular Molecular Structure Spiro Compounds - chemical synthesis Spiro Compounds - chemistry Stereoisomerism Sulfones - chemistry Vinyl Compounds - chemistry |
| title | Total Synthesis of (+)-Azaspiracid-1. An Exhibition of the Intricacies of Complex Molecule Synthesis |
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