A Highly Efficient Asymmetric Synthesis of Vernakalant
A novel synthesis of vernakalant is described. Using inexpensive and readily available reagents, the key transformations involve (1) an efficient zinc-amine-promoted etherification, (2) a highly stereoselective enzyme-catalyzed dynamic asymmetric transamination to set up the two contiguous chiral ce...
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| Veröffentlicht in: | Organic letters 2014-05, Vol.16 (10), p.2716-2719 |
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| container_end_page | 2719 |
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| container_issue | 10 |
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| container_title | Organic letters |
| container_volume | 16 |
| creator | Limanto, John Ashley, Eric R Yin, Jingjun Beutner, Gregory L Grau, Brendan T Kassim, Amude M Kim, Mary M Klapars, Artis Liu, Zhijian Strotman, Hallena R Truppo, Matthew D |
| description | A novel synthesis of vernakalant is described. Using inexpensive and readily available reagents, the key transformations involve (1) an efficient zinc-amine-promoted etherification, (2) a highly stereoselective enzyme-catalyzed dynamic asymmetric transamination to set up the two contiguous chiral centers in the cyclohexane ring, and (3) a pyrrolidine ring formation via alkyl-B(OH)2-catalyzed amidation and subsequent imide reduction. |
| doi_str_mv | 10.1021/ol501002a |
| format | Article |
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Using inexpensive and readily available reagents, the key transformations involve (1) an efficient zinc-amine-promoted etherification, (2) a highly stereoselective enzyme-catalyzed dynamic asymmetric transamination to set up the two contiguous chiral centers in the cyclohexane ring, and (3) a pyrrolidine ring formation via alkyl-B(OH)2-catalyzed amidation and subsequent imide reduction.</description><identifier>ISSN: 1523-7060</identifier><identifier>EISSN: 1523-7052</identifier><identifier>DOI: 10.1021/ol501002a</identifier><identifier>PMID: 24786635</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Amination ; Amines - chemistry ; Anisoles - chemical synthesis ; Anisoles - chemistry ; Catalysis ; Chlorides - chemistry ; Cyclohexanes ; Molecular Structure ; Pyrrolidines - chemical synthesis ; Pyrrolidines - chemistry ; Stereoisomerism ; Zinc Compounds - chemistry</subject><ispartof>Organic letters, 2014-05, Vol.16 (10), p.2716-2719</ispartof><rights>Copyright © 2014 American Chemical Society</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a315t-5ca0458b6559ab7199f796e20b100f94cf26050cd04350c143a1517879e3ac6e3</citedby><cites>FETCH-LOGICAL-a315t-5ca0458b6559ab7199f796e20b100f94cf26050cd04350c143a1517879e3ac6e3</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/ol501002a$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/ol501002a$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2751,27055,27903,27904,56716,56766</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24786635$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Limanto, John</creatorcontrib><creatorcontrib>Ashley, Eric R</creatorcontrib><creatorcontrib>Yin, Jingjun</creatorcontrib><creatorcontrib>Beutner, Gregory L</creatorcontrib><creatorcontrib>Grau, Brendan T</creatorcontrib><creatorcontrib>Kassim, Amude M</creatorcontrib><creatorcontrib>Kim, Mary M</creatorcontrib><creatorcontrib>Klapars, Artis</creatorcontrib><creatorcontrib>Liu, Zhijian</creatorcontrib><creatorcontrib>Strotman, Hallena R</creatorcontrib><creatorcontrib>Truppo, Matthew D</creatorcontrib><title>A Highly Efficient Asymmetric Synthesis of Vernakalant</title><title>Organic letters</title><addtitle>Org. Lett</addtitle><description>A novel synthesis of vernakalant is described. Using inexpensive and readily available reagents, the key transformations involve (1) an efficient zinc-amine-promoted etherification, (2) a highly stereoselective enzyme-catalyzed dynamic asymmetric transamination to set up the two contiguous chiral centers in the cyclohexane ring, and (3) a pyrrolidine ring formation via alkyl-B(OH)2-catalyzed amidation and subsequent imide reduction.</description><subject>Amination</subject><subject>Amines - chemistry</subject><subject>Anisoles - chemical synthesis</subject><subject>Anisoles - chemistry</subject><subject>Catalysis</subject><subject>Chlorides - chemistry</subject><subject>Cyclohexanes</subject><subject>Molecular Structure</subject><subject>Pyrrolidines - chemical synthesis</subject><subject>Pyrrolidines - chemistry</subject><subject>Stereoisomerism</subject><subject>Zinc Compounds - chemistry</subject><issn>1523-7060</issn><issn>1523-7052</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkDtPwzAUhS0EoqUw8AdQFiQYAtd2bMdjVRWKVImBx2o5rk1T8ih2MuTf16ilE9O5uvp0dM5B6BrDAwaCH9uKAQYg-gSNMSM0FcDI6fHmMEIXIWwAcPzIczQimcg5p2yM-DRZlF_rakjmzpWmtE2XTMNQ17bzpUnehqZb21CGpHXJp_WN_taVbrpLdOZ0FezVQSfo42n-Pluky9fnl9l0mWqKWZcyoyFjecEZk7oQWEonJLcEihjXycw4woGBWUFGo-CMasywyIW0VBtu6QTd7X23vv3pbehUXQZjq5jBtn1QsQ8TAucCInq_R41vQ_DWqa0va-0HhUH9zqSOM0X25mDbF7VdHcm_XSJwuwe0CWrT9rF4Ff4x2gG1Nmva</recordid><startdate>20140516</startdate><enddate>20140516</enddate><creator>Limanto, John</creator><creator>Ashley, Eric R</creator><creator>Yin, Jingjun</creator><creator>Beutner, Gregory L</creator><creator>Grau, Brendan T</creator><creator>Kassim, Amude M</creator><creator>Kim, Mary M</creator><creator>Klapars, Artis</creator><creator>Liu, Zhijian</creator><creator>Strotman, Hallena R</creator><creator>Truppo, Matthew D</creator><general>American Chemical Society</general><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>20140516</creationdate><title>A Highly Efficient Asymmetric Synthesis of Vernakalant</title><author>Limanto, John ; Ashley, Eric R ; Yin, Jingjun ; Beutner, Gregory L ; Grau, Brendan T ; Kassim, Amude M ; Kim, Mary M ; Klapars, Artis ; Liu, Zhijian ; Strotman, Hallena R ; Truppo, Matthew D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a315t-5ca0458b6559ab7199f796e20b100f94cf26050cd04350c143a1517879e3ac6e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Amination</topic><topic>Amines - chemistry</topic><topic>Anisoles - chemical synthesis</topic><topic>Anisoles - chemistry</topic><topic>Catalysis</topic><topic>Chlorides - chemistry</topic><topic>Cyclohexanes</topic><topic>Molecular Structure</topic><topic>Pyrrolidines - chemical synthesis</topic><topic>Pyrrolidines - chemistry</topic><topic>Stereoisomerism</topic><topic>Zinc Compounds - chemistry</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Limanto, John</creatorcontrib><creatorcontrib>Ashley, Eric R</creatorcontrib><creatorcontrib>Yin, Jingjun</creatorcontrib><creatorcontrib>Beutner, Gregory L</creatorcontrib><creatorcontrib>Grau, Brendan T</creatorcontrib><creatorcontrib>Kassim, Amude M</creatorcontrib><creatorcontrib>Kim, Mary M</creatorcontrib><creatorcontrib>Klapars, Artis</creatorcontrib><creatorcontrib>Liu, Zhijian</creatorcontrib><creatorcontrib>Strotman, Hallena R</creatorcontrib><creatorcontrib>Truppo, Matthew D</creatorcontrib><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>Organic letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Limanto, John</au><au>Ashley, Eric R</au><au>Yin, Jingjun</au><au>Beutner, Gregory L</au><au>Grau, Brendan T</au><au>Kassim, Amude M</au><au>Kim, Mary M</au><au>Klapars, Artis</au><au>Liu, Zhijian</au><au>Strotman, Hallena R</au><au>Truppo, Matthew D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Highly Efficient Asymmetric Synthesis of Vernakalant</atitle><jtitle>Organic letters</jtitle><addtitle>Org. 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| fulltext | fulltext |
| identifier | ISSN: 1523-7060 |
| ispartof | Organic letters, 2014-05, Vol.16 (10), p.2716-2719 |
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| language | eng |
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| source | MEDLINE; ACS Publications |
| subjects | Amination Amines - chemistry Anisoles - chemical synthesis Anisoles - chemistry Catalysis Chlorides - chemistry Cyclohexanes Molecular Structure Pyrrolidines - chemical synthesis Pyrrolidines - chemistry Stereoisomerism Zinc Compounds - chemistry |
| title | A Highly Efficient Asymmetric Synthesis of Vernakalant |
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