Development of a Third-Generation Total Synthesis of (+)-Discodermolide: An Expedient Still−Gennari-Type Fragment Coupling Utilizing an Advanced β-Ketophosphonate
A novel total synthesis of the complex polyketide discodermolide, a promising anticancer agent of marine sponge origin, has been completed in 11.1% overall yield over 21 linear steps. This third-generation approach features an unprecedented Still−Gennari-type HWE olefination reaction between advance...
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| Veröffentlicht in: | Journal of organic chemistry 2005-07, Vol.70 (14), p.5494-5507 |
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| container_title | Journal of organic chemistry |
| container_volume | 70 |
| creator | Paterson, Ian Lyothier, Isabelle |
| description | A novel total synthesis of the complex polyketide discodermolide, a promising anticancer agent of marine sponge origin, has been completed in 11.1% overall yield over 21 linear steps. This third-generation approach features an unprecedented Still−Gennari-type HWE olefination reaction between advanced C1−C8 β-ketophosphonate 61 and C9−C24 aldehyde 7, introducing the (8Z)-alkene with 10:1 selectivity. The stereotetrad found in the C1−C8 subunit 61 was established via a highly diastereoselective boron-mediated aldol reaction/in situ reduction between ketone (S)-8 and 3-benzyloxypropanal. The (7S)-configuration was installed by the reduction of enone 73 with K-Selectride. |
| doi_str_mv | 10.1021/jo050481a |
| format | Article |
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Org. Chem</addtitle><description>A novel total synthesis of the complex polyketide discodermolide, a promising anticancer agent of marine sponge origin, has been completed in 11.1% overall yield over 21 linear steps. This third-generation approach features an unprecedented Still−Gennari-type HWE olefination reaction between advanced C1−C8 β-ketophosphonate 61 and C9−C24 aldehyde 7, introducing the (8Z)-alkene with 10:1 selectivity. The stereotetrad found in the C1−C8 subunit 61 was established via a highly diastereoselective boron-mediated aldol reaction/in situ reduction between ketone (S)-8 and 3-benzyloxypropanal. The (7S)-configuration was installed by the reduction of enone 73 with K-Selectride.</description><subject>Aldehydes - chemistry</subject><subject>Alkanes - chemical synthesis</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Boron - chemistry</subject><subject>Carbamates - chemical synthesis</subject><subject>Chemistry</subject><subject>Exact sciences and technology</subject><subject>Heterocyclic compounds</subject><subject>Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives</subject><subject>Ketones - chemistry</subject><subject>Lactones - chemical synthesis</subject><subject>Models, Chemical</subject><subject>Organic chemistry</subject><subject>Organophosphonates - chemical synthesis</subject><subject>Oxidation-Reduction</subject><subject>Preparations and properties</subject><subject>Pyrones</subject><subject>Stereoisomerism</subject><issn>0022-3263</issn><issn>1520-6904</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkcFu0zAcxi0EYmVw4AWQLyAmZLDjOIm5Ve06EJNAanaO3Pif1SOxg51MKyeOcOUpOPMgPMSeBJdW6wVLli37p8-fvw-hp4y-ZjRhb64cFTQtmLqHJkwklGSSpvfRhNIkITzJ-BF6FMIVjUMI8RAdMSELyTmboF9zuIbW9R3YAbsGK1yujdfkDCx4NRhncekG1eLlxg5rCCZsqZevTsjchNpp8J1rjYa3t99-4KnFpzc9aLMVWw6mbW-__4xKVnlDyk0PeOHV5b-nZm7sW2Mv8UXEzNftTlk81dfK1qDxn9_kAwyuX7sQp1UDPEYPGtUGeLJfj9HF4rScvSPnH8_ez6bnRPGCDaRo8pqLAmpgPGsE09BoJlkimVjJOolHtOBFoldSNJBkOoZTA3AQLE2lgIYfoxc73d67LyOEoeriR6FtlQU3hirLpWQpoxE82YG1dyF4aKrem075TcVota2luqslss_2ouOqA30g9z1E4PkeUKFWbeNjDCYcuEymImdZ5MiOM2GAm7t75T9HYzwXVflpWSXzxZzLjFX5QVfVIfoZvY3Z_cfgXyCBtEo</recordid><startdate>20050708</startdate><enddate>20050708</enddate><creator>Paterson, Ian</creator><creator>Lyothier, Isabelle</creator><general>American Chemical Society</general><scope>BSCLL</scope><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>20050708</creationdate><title>Development of a Third-Generation Total Synthesis of (+)-Discodermolide: An Expedient Still−Gennari-Type Fragment Coupling Utilizing an Advanced β-Ketophosphonate</title><author>Paterson, Ian ; Lyothier, Isabelle</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a381t-8f7c358ece136f51defd1912915b9c26f508382db95fe26d263cee3e514495ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Aldehydes - chemistry</topic><topic>Alkanes - chemical synthesis</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Boron - chemistry</topic><topic>Carbamates - chemical synthesis</topic><topic>Chemistry</topic><topic>Exact sciences and technology</topic><topic>Heterocyclic compounds</topic><topic>Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives</topic><topic>Ketones - chemistry</topic><topic>Lactones - chemical synthesis</topic><topic>Models, Chemical</topic><topic>Organic chemistry</topic><topic>Organophosphonates - chemical synthesis</topic><topic>Oxidation-Reduction</topic><topic>Preparations and properties</topic><topic>Pyrones</topic><topic>Stereoisomerism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Paterson, Ian</creatorcontrib><creatorcontrib>Lyothier, Isabelle</creatorcontrib><collection>Istex</collection><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>Paterson, Ian</au><au>Lyothier, Isabelle</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Development of a Third-Generation Total Synthesis of (+)-Discodermolide: An Expedient Still−Gennari-Type Fragment Coupling Utilizing an Advanced β-Ketophosphonate</atitle><jtitle>Journal of organic chemistry</jtitle><addtitle>J. Org. Chem</addtitle><date>2005-07-08</date><risdate>2005</risdate><volume>70</volume><issue>14</issue><spage>5494</spage><epage>5507</epage><pages>5494-5507</pages><issn>0022-3263</issn><eissn>1520-6904</eissn><coden>JOCEAH</coden><abstract>A novel total synthesis of the complex polyketide discodermolide, a promising anticancer agent of marine sponge origin, has been completed in 11.1% overall yield over 21 linear steps. This third-generation approach features an unprecedented Still−Gennari-type HWE olefination reaction between advanced C1−C8 β-ketophosphonate 61 and C9−C24 aldehyde 7, introducing the (8Z)-alkene with 10:1 selectivity. The stereotetrad found in the C1−C8 subunit 61 was established via a highly diastereoselective boron-mediated aldol reaction/in situ reduction between ketone (S)-8 and 3-benzyloxypropanal. 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| ispartof | Journal of organic chemistry, 2005-07, Vol.70 (14), p.5494-5507 |
| issn | 0022-3263 1520-6904 |
| language | eng |
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| source | MEDLINE; American Chemical Society (ACS) Journals |
| subjects | Aldehydes - chemistry Alkanes - chemical synthesis Antineoplastic Agents - chemical synthesis Boron - chemistry Carbamates - chemical synthesis Chemistry Exact sciences and technology Heterocyclic compounds Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives Ketones - chemistry Lactones - chemical synthesis Models, Chemical Organic chemistry Organophosphonates - chemical synthesis Oxidation-Reduction Preparations and properties Pyrones Stereoisomerism |
| title | Development of a Third-Generation Total Synthesis of (+)-Discodermolide: An Expedient Still−Gennari-Type Fragment Coupling Utilizing an Advanced β-Ketophosphonate |
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