New reactions and processes for the efficient synthesis of a HCV NS5b prodrug
Herein we describe the route scouting and process development efforts toward a green and sustainable synthesis of the HCV NS5b cyclic prodrug nucleoside (CPN) 1 . Through the discovery and development of a crystallization-induced dynamic resolution and a novel chemo- and stereo-selective phosphoryla...
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| Veröffentlicht in: | Green chemistry : an international journal and green chemistry resource : GC 2018, Vol.2 (11), p.2519-2525 |
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| container_issue | 11 |
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| container_title | Green chemistry : an international journal and green chemistry resource : GC |
| container_volume | 2 |
| creator | Orr, Robert K McCabe Dunn, Jamie M Nolting, Andrew Hyde, Alan M Ashley, Eric R Leone, Joseph Sirota, Eric Jurica, Jon A Gibson, Andrew Wise, Christopher Oliver, Steven Ruck, Rebecca T |
| description | Herein we describe the route scouting and process development efforts toward a green and sustainable synthesis of the HCV NS5b cyclic prodrug nucleoside (CPN)
1
. Through the discovery and development of a crystallization-induced dynamic resolution and a novel chemo- and stereo-selective phosphorylation reaction, we eliminated costly chromatographies and protecting group manipulations utilized in the initial approaches to this compound and implemented a highly streamlined and sustainable approach to the target molecule. We demonstrate how these improvements impact the PMI of the API on the kilogram scale and compare our work to the PMI of APIs of similar complexity.
The evolution of synthetic chemistry approaches towards a green and sustainable synthesis of a HCV NS5b cyclic prodrug nucleoside (CPN) is described. |
| doi_str_mv | 10.1039/c8gc00102b |
| format | Article |
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1
. Through the discovery and development of a crystallization-induced dynamic resolution and a novel chemo- and stereo-selective phosphorylation reaction, we eliminated costly chromatographies and protecting group manipulations utilized in the initial approaches to this compound and implemented a highly streamlined and sustainable approach to the target molecule. We demonstrate how these improvements impact the PMI of the API on the kilogram scale and compare our work to the PMI of APIs of similar complexity.
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1
. Through the discovery and development of a crystallization-induced dynamic resolution and a novel chemo- and stereo-selective phosphorylation reaction, we eliminated costly chromatographies and protecting group manipulations utilized in the initial approaches to this compound and implemented a highly streamlined and sustainable approach to the target molecule. We demonstrate how these improvements impact the PMI of the API on the kilogram scale and compare our work to the PMI of APIs of similar complexity.
The evolution of synthetic chemistry approaches towards a green and sustainable synthesis of a HCV NS5b cyclic prodrug nucleoside (CPN) is described.</description><subject>Chemical synthesis</subject><subject>Crystallization</subject><subject>Green chemistry</subject><subject>Molecular chains</subject><subject>Phosphorylation</subject><subject>RNA-directed RNA polymerase</subject><subject>Sustainable development</subject><issn>1463-9262</issn><issn>1463-9270</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNpFkE1Lw0AQhhdRsFYv3oUFb0J0NrvZ3Rw1aCvUevDjGjab2ZqiSd1Jkf57o5V6mmF43nnhYexUwKUAmV95u_AAAtJqj42E0jLJUwP7u12nh-yIaDkwwmg1Yg9z_OIRne-briXu2pqvYueRCImHLvL-DTmG0PgG257Tph0O1BDvAnd8Wrzy-VNW_WTquF4cs4Pg3glP_uaYvdzdPhfTZPY4uS-uZ4mXwvaJsgDOKOtsnYEEYaQwxoOUWdAm84hBQ6UcVEGARpMbVJi6WjsUqEGgHLPz7d-h93ON1JfLbh3bobJMQeWZTU0uB-piS_nYEUUM5So2Hy5uSgHlj66ysJPiV9fNAJ9t4Uh-x_3rlN8KvWUN</recordid><startdate>2018</startdate><enddate>2018</enddate><creator>Orr, Robert K</creator><creator>McCabe Dunn, Jamie M</creator><creator>Nolting, Andrew</creator><creator>Hyde, Alan M</creator><creator>Ashley, Eric R</creator><creator>Leone, Joseph</creator><creator>Sirota, Eric</creator><creator>Jurica, Jon A</creator><creator>Gibson, Andrew</creator><creator>Wise, Christopher</creator><creator>Oliver, Steven</creator><creator>Ruck, Rebecca T</creator><general>Royal Society of Chemistry</general><scope>AAYXX</scope><scope>CITATION</scope><scope>7SR</scope><scope>7ST</scope><scope>7U6</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>JG9</scope><orcidid>https://orcid.org/0000-0003-1103-8859</orcidid><orcidid>https://orcid.org/0000-0001-9980-9675</orcidid><orcidid>https://orcid.org/0000-0002-0513-3342</orcidid><orcidid>https://orcid.org/0000-0003-0779-9284</orcidid><orcidid>https://orcid.org/0000-0001-8584-4808</orcidid><orcidid>https://orcid.org/0000-0002-0709-595X</orcidid></search><sort><creationdate>2018</creationdate><title>New reactions and processes for the efficient synthesis of a HCV NS5b prodrug</title><author>Orr, Robert K ; McCabe Dunn, Jamie M ; Nolting, Andrew ; Hyde, Alan M ; Ashley, Eric R ; Leone, Joseph ; Sirota, Eric ; Jurica, Jon A ; Gibson, Andrew ; Wise, Christopher ; Oliver, Steven ; Ruck, Rebecca T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c318t-4800a748a8d5030173177c0335f675ceef60b4a0bf106e797e4e2ad6ae1e601e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Chemical synthesis</topic><topic>Crystallization</topic><topic>Green chemistry</topic><topic>Molecular chains</topic><topic>Phosphorylation</topic><topic>RNA-directed RNA polymerase</topic><topic>Sustainable development</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Orr, Robert K</creatorcontrib><creatorcontrib>McCabe Dunn, Jamie M</creatorcontrib><creatorcontrib>Nolting, Andrew</creatorcontrib><creatorcontrib>Hyde, Alan M</creatorcontrib><creatorcontrib>Ashley, Eric R</creatorcontrib><creatorcontrib>Leone, Joseph</creatorcontrib><creatorcontrib>Sirota, Eric</creatorcontrib><creatorcontrib>Jurica, Jon A</creatorcontrib><creatorcontrib>Gibson, Andrew</creatorcontrib><creatorcontrib>Wise, Christopher</creatorcontrib><creatorcontrib>Oliver, Steven</creatorcontrib><creatorcontrib>Ruck, Rebecca T</creatorcontrib><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Environment Abstracts</collection><collection>Sustainability Science Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Materials Research Database</collection><jtitle>Green chemistry : an international journal and green chemistry resource : GC</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Orr, Robert K</au><au>McCabe Dunn, Jamie M</au><au>Nolting, Andrew</au><au>Hyde, Alan M</au><au>Ashley, Eric R</au><au>Leone, Joseph</au><au>Sirota, Eric</au><au>Jurica, Jon A</au><au>Gibson, Andrew</au><au>Wise, Christopher</au><au>Oliver, Steven</au><au>Ruck, Rebecca T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New reactions and processes for the efficient synthesis of a HCV NS5b prodrug</atitle><jtitle>Green chemistry : an international journal and green chemistry resource : GC</jtitle><date>2018</date><risdate>2018</risdate><volume>2</volume><issue>11</issue><spage>2519</spage><epage>2525</epage><pages>2519-2525</pages><issn>1463-9262</issn><eissn>1463-9270</eissn><abstract>Herein we describe the route scouting and process development efforts toward a green and sustainable synthesis of the HCV NS5b cyclic prodrug nucleoside (CPN)
1
. Through the discovery and development of a crystallization-induced dynamic resolution and a novel chemo- and stereo-selective phosphorylation reaction, we eliminated costly chromatographies and protecting group manipulations utilized in the initial approaches to this compound and implemented a highly streamlined and sustainable approach to the target molecule. We demonstrate how these improvements impact the PMI of the API on the kilogram scale and compare our work to the PMI of APIs of similar complexity.
The evolution of synthetic chemistry approaches towards a green and sustainable synthesis of a HCV NS5b cyclic prodrug nucleoside (CPN) is described.</abstract><cop>Cambridge</cop><pub>Royal Society of Chemistry</pub><doi>10.1039/c8gc00102b</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-1103-8859</orcidid><orcidid>https://orcid.org/0000-0001-9980-9675</orcidid><orcidid>https://orcid.org/0000-0002-0513-3342</orcidid><orcidid>https://orcid.org/0000-0003-0779-9284</orcidid><orcidid>https://orcid.org/0000-0001-8584-4808</orcidid><orcidid>https://orcid.org/0000-0002-0709-595X</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1463-9262 |
| ispartof | Green chemistry : an international journal and green chemistry resource : GC, 2018, Vol.2 (11), p.2519-2525 |
| issn | 1463-9262 1463-9270 |
| language | eng |
| recordid | cdi_rsc_primary_c8gc00102b |
| source | Royal Society Of Chemistry Journals 2008-; Alma/SFX Local Collection |
| subjects | Chemical synthesis Crystallization Green chemistry Molecular chains Phosphorylation RNA-directed RNA polymerase Sustainable development |
| title | New reactions and processes for the efficient synthesis of a HCV NS5b prodrug |
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