An Efficient and Highly Diastereoselective Synthesis of GSK1265744, a Potent HIV Integrase Inhibitor
A novel synthesis of GSK1265744, a potent HIV integrase inhibitor, is described. The synthesis is highlighted by an efficient construction of the densely functionalized pyridinone core as well as a highly diastereoselective formation of the acyl oxazolidine moiety. The latter exploits the target mol...
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| Veröffentlicht in: | Organic letters 2015-02, Vol.17 (3), p.564-567 |
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| container_title | Organic letters |
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| creator | Wang, Huan Kowalski, Matthew D Lakdawala, Ami S Vogt, Frederick G Wu, Lianming |
| description | A novel synthesis of GSK1265744, a potent HIV integrase inhibitor, is described. The synthesis is highlighted by an efficient construction of the densely functionalized pyridinone core as well as a highly diastereoselective formation of the acyl oxazolidine moiety. The latter exploits the target molecule’s ability to chelate to Mg2+, a key feature in the integrase inhibitor’s mechanism of action. |
| doi_str_mv | 10.1021/ol503580t |
| format | Article |
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The synthesis is highlighted by an efficient construction of the densely functionalized pyridinone core as well as a highly diastereoselective formation of the acyl oxazolidine moiety. The latter exploits the target molecule’s ability to chelate to Mg2+, a key feature in the integrase inhibitor’s mechanism of action.</description><identifier>ISSN: 1523-7060</identifier><identifier>EISSN: 1523-7052</identifier><identifier>DOI: 10.1021/ol503580t</identifier><identifier>PMID: 25615910</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Chelating Agents - chemistry ; Chelating Agents - metabolism ; HIV Integrase Inhibitors - chemical synthesis ; HIV Integrase Inhibitors - chemistry ; HIV Integrase Inhibitors - pharmacology ; Magnesium - chemistry ; Magnesium - metabolism ; Molecular Structure ; Pyridones - chemical synthesis ; Pyridones - chemistry ; Pyridones - pharmacology ; Stereoisomerism ; Structure-Activity Relationship</subject><ispartof>Organic letters, 2015-02, Vol.17 (3), p.564-567</ispartof><rights>Copyright © 2015 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a315t-2f905e9127c064c4fce16e04f16a1c4605544e682ee805c2f509aba0b8e5e8e23</citedby><cites>FETCH-LOGICAL-a315t-2f905e9127c064c4fce16e04f16a1c4605544e682ee805c2f509aba0b8e5e8e23</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/ol503580t$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ol503580t$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2756,27067,27915,27916,56729,56779</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25615910$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Huan</creatorcontrib><creatorcontrib>Kowalski, Matthew D</creatorcontrib><creatorcontrib>Lakdawala, Ami S</creatorcontrib><creatorcontrib>Vogt, Frederick G</creatorcontrib><creatorcontrib>Wu, Lianming</creatorcontrib><title>An Efficient and Highly Diastereoselective Synthesis of GSK1265744, a Potent HIV Integrase Inhibitor</title><title>Organic letters</title><addtitle>Org. 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| identifier | ISSN: 1523-7060 |
| ispartof | Organic letters, 2015-02, Vol.17 (3), p.564-567 |
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| language | eng |
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| source | MEDLINE; American Chemical Society Publications |
| subjects | Chelating Agents - chemistry Chelating Agents - metabolism HIV Integrase Inhibitors - chemical synthesis HIV Integrase Inhibitors - chemistry HIV Integrase Inhibitors - pharmacology Magnesium - chemistry Magnesium - metabolism Molecular Structure Pyridones - chemical synthesis Pyridones - chemistry Pyridones - pharmacology Stereoisomerism Structure-Activity Relationship |
| title | An Efficient and Highly Diastereoselective Synthesis of GSK1265744, a Potent HIV Integrase Inhibitor |
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