Stereoselective semi-synthesis of the neuroprotective natural product, serofendic acid
We have recently demonstrated a synthetic biology-enabled semi-synthesis of the potent neuroprotective compound, serofendic acid. An engineered bacterium produces ent -atis-16-en-19-oic acid, which has six of eight chiral carbons configured with the appropriate stereochemistry. Setting the configura...
Gespeichert in:
| Veröffentlicht in: | MedChemComm 2019-06, Vol.1 (6), p.951-96 |
|---|---|
| Hauptverfasser: | , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 96 |
|---|---|
| container_issue | 6 |
| container_start_page | 951 |
| container_title | MedChemComm |
| container_volume | 1 |
| creator | Perusse, Dimitri Smanski, Michael J |
| description | We have recently demonstrated a synthetic biology-enabled semi-synthesis of the potent neuroprotective compound, serofendic acid. An engineered bacterium produces
ent
-atis-16-en-19-oic acid, which has six of eight chiral carbons configured with the appropriate stereochemistry. Setting the configuration of the C15 hydroxyl group and C16 methylene is a critical step that occurs late in each published total or formal synthesis. Here we explore the use of alternative reducing reagents, stereochemical directing agents, reaction order, and product recycling to improve the diastereoselectivity of this step. We find that installing and oxidizing the C17 methylsulfide prior to reducing the C15 ketone provides the greatest yield of the desired C15,C16 diastereomer. This represents an improved total synthesis of serofendic acid.
Our synthesis of neuroprotectant serofendic acid from biosourced
ent
-atis-16-en-19-oic acid represents the best route to date. |
| doi_str_mv | 10.1039/c9md00145j |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_rsc_p</sourceid><recordid>TN_cdi_proquest_miscellaneous_2258152138</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2258152138</sourcerecordid><originalsourceid>FETCH-LOGICAL-c454t-6cf5948e196fec17cd08c4963007aeb288bd5e24c0776296e3f2abfd9cf4416b3</originalsourceid><addsrcrecordid>eNp9kb1vFDEQxS0EIlFIQw9aRIMQC_6-dYOELgESBVEkobW89pj4tLu-2N5I-e9juOMCFJlmRp7fPD3rIfSc4PcEM_XBqtFhTLhYPUL7FHPcUkHI492M2R46zHmFazHadYo_RXuMsHqr2D76cV4gQcwwgC3hBpoMY2jz7VSuIIfcRN_UqZlgTnGdYtlSkylzMkNTn9xsy7t6lqKHyQXbGBvcM_TEmyHD4bYfoMvPxxfLr-3Z9y8ny09nreWCl1ZaLxTvgCjpwZKFdbizXEmG8cJAX-32TgDlFi8WkioJzFPTe6es55zInh2gjxvd9dyP4CxMpdrS6xRGk251NEH_u5nClf4Zb7QUSigpq8CbrUCK1zPkoseQLQyDmSDOWVMqOiIoYV1FX_-HruKcpvq9SnFGBeWYV-rthrIp5pzA78wQrH8lppfq29HvxE4r_PJv-zv0Tz4VeLUBUra77X3keu18ZV48xLA7Dien5w</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2243252404</pqid></control><display><type>article</type><title>Stereoselective semi-synthesis of the neuroprotective natural product, serofendic acid</title><source>Royal Society Of Chemistry Journals 2008-</source><source>PubMed Central</source><creator>Perusse, Dimitri ; Smanski, Michael J</creator><creatorcontrib>Perusse, Dimitri ; Smanski, Michael J</creatorcontrib><description>We have recently demonstrated a synthetic biology-enabled semi-synthesis of the potent neuroprotective compound, serofendic acid. An engineered bacterium produces
ent
-atis-16-en-19-oic acid, which has six of eight chiral carbons configured with the appropriate stereochemistry. Setting the configuration of the C15 hydroxyl group and C16 methylene is a critical step that occurs late in each published total or formal synthesis. Here we explore the use of alternative reducing reagents, stereochemical directing agents, reaction order, and product recycling to improve the diastereoselectivity of this step. We find that installing and oxidizing the C17 methylsulfide prior to reducing the C15 ketone provides the greatest yield of the desired C15,C16 diastereomer. This represents an improved total synthesis of serofendic acid.
Our synthesis of neuroprotectant serofendic acid from biosourced
ent
-atis-16-en-19-oic acid represents the best route to date.</description><identifier>ISSN: 2040-2503</identifier><identifier>ISSN: 2040-2511</identifier><identifier>EISSN: 2040-2511</identifier><identifier>DOI: 10.1039/c9md00145j</identifier><identifier>PMID: 31303993</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Acids ; Chemical reduction ; Chemistry ; Hydroxyl groups ; Natural products ; Neuroprotection ; Oxidation ; Reagents ; Semisynthesis ; Stereochemistry ; Stereoselectivity ; Synthesis</subject><ispartof>MedChemComm, 2019-06, Vol.1 (6), p.951-96</ispartof><rights>Copyright Royal Society of Chemistry 2019</rights><rights>This journal is © The Royal Society of Chemistry 2019 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c454t-6cf5948e196fec17cd08c4963007aeb288bd5e24c0776296e3f2abfd9cf4416b3</citedby><cites>FETCH-LOGICAL-c454t-6cf5948e196fec17cd08c4963007aeb288bd5e24c0776296e3f2abfd9cf4416b3</cites><orcidid>0000-0001-8115-7883 ; 0000-0002-6029-8326</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595966/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595966/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31303993$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Perusse, Dimitri</creatorcontrib><creatorcontrib>Smanski, Michael J</creatorcontrib><title>Stereoselective semi-synthesis of the neuroprotective natural product, serofendic acid</title><title>MedChemComm</title><addtitle>Medchemcomm</addtitle><description>We have recently demonstrated a synthetic biology-enabled semi-synthesis of the potent neuroprotective compound, serofendic acid. An engineered bacterium produces
ent
-atis-16-en-19-oic acid, which has six of eight chiral carbons configured with the appropriate stereochemistry. Setting the configuration of the C15 hydroxyl group and C16 methylene is a critical step that occurs late in each published total or formal synthesis. Here we explore the use of alternative reducing reagents, stereochemical directing agents, reaction order, and product recycling to improve the diastereoselectivity of this step. We find that installing and oxidizing the C17 methylsulfide prior to reducing the C15 ketone provides the greatest yield of the desired C15,C16 diastereomer. This represents an improved total synthesis of serofendic acid.
Our synthesis of neuroprotectant serofendic acid from biosourced
ent
-atis-16-en-19-oic acid represents the best route to date.</description><subject>Acids</subject><subject>Chemical reduction</subject><subject>Chemistry</subject><subject>Hydroxyl groups</subject><subject>Natural products</subject><subject>Neuroprotection</subject><subject>Oxidation</subject><subject>Reagents</subject><subject>Semisynthesis</subject><subject>Stereochemistry</subject><subject>Stereoselectivity</subject><subject>Synthesis</subject><issn>2040-2503</issn><issn>2040-2511</issn><issn>2040-2511</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kb1vFDEQxS0EIlFIQw9aRIMQC_6-dYOELgESBVEkobW89pj4tLu-2N5I-e9juOMCFJlmRp7fPD3rIfSc4PcEM_XBqtFhTLhYPUL7FHPcUkHI492M2R46zHmFazHadYo_RXuMsHqr2D76cV4gQcwwgC3hBpoMY2jz7VSuIIfcRN_UqZlgTnGdYtlSkylzMkNTn9xsy7t6lqKHyQXbGBvcM_TEmyHD4bYfoMvPxxfLr-3Z9y8ny09nreWCl1ZaLxTvgCjpwZKFdbizXEmG8cJAX-32TgDlFi8WkioJzFPTe6es55zInh2gjxvd9dyP4CxMpdrS6xRGk251NEH_u5nClf4Zb7QUSigpq8CbrUCK1zPkoseQLQyDmSDOWVMqOiIoYV1FX_-HruKcpvq9SnFGBeWYV-rthrIp5pzA78wQrH8lppfq29HvxE4r_PJv-zv0Tz4VeLUBUra77X3keu18ZV48xLA7Dien5w</recordid><startdate>20190601</startdate><enddate>20190601</enddate><creator>Perusse, Dimitri</creator><creator>Smanski, Michael J</creator><general>Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7T5</scope><scope>7T7</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-8115-7883</orcidid><orcidid>https://orcid.org/0000-0002-6029-8326</orcidid></search><sort><creationdate>20190601</creationdate><title>Stereoselective semi-synthesis of the neuroprotective natural product, serofendic acid</title><author>Perusse, Dimitri ; Smanski, Michael J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c454t-6cf5948e196fec17cd08c4963007aeb288bd5e24c0776296e3f2abfd9cf4416b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Acids</topic><topic>Chemical reduction</topic><topic>Chemistry</topic><topic>Hydroxyl groups</topic><topic>Natural products</topic><topic>Neuroprotection</topic><topic>Oxidation</topic><topic>Reagents</topic><topic>Semisynthesis</topic><topic>Stereochemistry</topic><topic>Stereoselectivity</topic><topic>Synthesis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Perusse, Dimitri</creatorcontrib><creatorcontrib>Smanski, Michael J</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>MedChemComm</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Perusse, Dimitri</au><au>Smanski, Michael J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Stereoselective semi-synthesis of the neuroprotective natural product, serofendic acid</atitle><jtitle>MedChemComm</jtitle><addtitle>Medchemcomm</addtitle><date>2019-06-01</date><risdate>2019</risdate><volume>1</volume><issue>6</issue><spage>951</spage><epage>96</epage><pages>951-96</pages><issn>2040-2503</issn><issn>2040-2511</issn><eissn>2040-2511</eissn><abstract>We have recently demonstrated a synthetic biology-enabled semi-synthesis of the potent neuroprotective compound, serofendic acid. An engineered bacterium produces
ent
-atis-16-en-19-oic acid, which has six of eight chiral carbons configured with the appropriate stereochemistry. Setting the configuration of the C15 hydroxyl group and C16 methylene is a critical step that occurs late in each published total or formal synthesis. Here we explore the use of alternative reducing reagents, stereochemical directing agents, reaction order, and product recycling to improve the diastereoselectivity of this step. We find that installing and oxidizing the C17 methylsulfide prior to reducing the C15 ketone provides the greatest yield of the desired C15,C16 diastereomer. This represents an improved total synthesis of serofendic acid.
Our synthesis of neuroprotectant serofendic acid from biosourced
ent
-atis-16-en-19-oic acid represents the best route to date.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>31303993</pmid><doi>10.1039/c9md00145j</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-8115-7883</orcidid><orcidid>https://orcid.org/0000-0002-6029-8326</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2040-2503 |
| ispartof | MedChemComm, 2019-06, Vol.1 (6), p.951-96 |
| issn | 2040-2503 2040-2511 2040-2511 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2258152138 |
| source | Royal Society Of Chemistry Journals 2008-; PubMed Central |
| subjects | Acids Chemical reduction Chemistry Hydroxyl groups Natural products Neuroprotection Oxidation Reagents Semisynthesis Stereochemistry Stereoselectivity Synthesis |
| title | Stereoselective semi-synthesis of the neuroprotective natural product, serofendic acid |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T19%3A01%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_rsc_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Stereoselective%20semi-synthesis%20of%20the%20neuroprotective%20natural%20product,%20serofendic%20acid&rft.jtitle=MedChemComm&rft.au=Perusse,%20Dimitri&rft.date=2019-06-01&rft.volume=1&rft.issue=6&rft.spage=951&rft.epage=96&rft.pages=951-96&rft.issn=2040-2503&rft.eissn=2040-2511&rft_id=info:doi/10.1039/c9md00145j&rft_dat=%3Cproquest_rsc_p%3E2258152138%3C/proquest_rsc_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2243252404&rft_id=info:pmid/31303993&rfr_iscdi=true |