Discovery of florylpicoxamid, a mimic of a macrocyclic natural product
[Display omitted] Natural products have routinely been used both as sources of and inspiration for new crop protection active ingredients. The natural product UK-2A has potent anti-fungal activity but lacks key attributes for field translation. Post-fermentation conversion of UK-2A to fenpicoxamid r...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2021-11, Vol.50, p.116455-116455, Article 116455 |
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| creator | Meyer, Kevin G. Bravo-Altamirano, Karla Herrick, Jessica Loy, Brian A. Yao, Chenglin Nugent, Ben Buchan, Zachary Daeuble, John F. Heemstra, Ron Jones, David M. Wilmot, Jeremy Lu, Yu DeKorver, Kyle DeLorbe, Johnathan Rigoli, Jared |
| description | [Display omitted]
Natural products have routinely been used both as sources of and inspiration for new crop protection active ingredients. The natural product UK-2A has potent anti-fungal activity but lacks key attributes for field translation. Post-fermentation conversion of UK-2A to fenpicoxamid resulted in an active ingredient with a new target site of action for cereal and banana pathogens. Here we demonstrate the creation of a synthetic variant of fenpicoxamid via identification of the structural elements of UK-2A that are needed for anti-fungal activity. Florylpicoxamid is a non-macrocyclic active ingredient bearing two fewer stereocenters than fenpicoxamid, controls a broad spectrum of fungal diseases at low use rates and has a concise, scalable route which is aligned with green chemistry principles. The development of florylpicoxamid represents the first example of using a stepwise deconstruction of a macrocyclic natural product to design a fully synthetic crop protection active ingredient. |
| doi_str_mv | 10.1016/j.bmc.2021.116455 |
| format | Article |
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Natural products have routinely been used both as sources of and inspiration for new crop protection active ingredients. The natural product UK-2A has potent anti-fungal activity but lacks key attributes for field translation. Post-fermentation conversion of UK-2A to fenpicoxamid resulted in an active ingredient with a new target site of action for cereal and banana pathogens. Here we demonstrate the creation of a synthetic variant of fenpicoxamid via identification of the structural elements of UK-2A that are needed for anti-fungal activity. Florylpicoxamid is a non-macrocyclic active ingredient bearing two fewer stereocenters than fenpicoxamid, controls a broad spectrum of fungal diseases at low use rates and has a concise, scalable route which is aligned with green chemistry principles. The development of florylpicoxamid represents the first example of using a stepwise deconstruction of a macrocyclic natural product to design a fully synthetic crop protection active ingredient.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2021.116455</identifier><identifier>PMID: 34757295</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Antifungal Agents - chemical synthesis ; Antifungal Agents - chemistry ; Antifungal Agents - pharmacology ; Ascomycota - drug effects ; Biological Products - chemical synthesis ; Biological Products - chemistry ; Biological Products - pharmacology ; Crop protection ; Disease control ; Dose-Response Relationship, Drug ; Drug Discovery ; Florylpicoxamid ; Fungicide ; Macrocyclic Compounds - chemical synthesis ; Macrocyclic Compounds - chemistry ; Macrocyclic Compounds - pharmacology ; Microbial Sensitivity Tests ; Molecular Structure ; Natural product mimic ; Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry, 2021-11, Vol.50, p.116455-116455, Article 116455</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-ad60d7c2fbd63e252ce15f9dfed8cdf2840d1065e7deedafb33cd7a873a9cb443</citedby><cites>FETCH-LOGICAL-c353t-ad60d7c2fbd63e252ce15f9dfed8cdf2840d1065e7deedafb33cd7a873a9cb443</cites><orcidid>0000-0001-7751-5027 ; 0000-0003-1235-3463</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmc.2021.116455$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34757295$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meyer, Kevin G.</creatorcontrib><creatorcontrib>Bravo-Altamirano, Karla</creatorcontrib><creatorcontrib>Herrick, Jessica</creatorcontrib><creatorcontrib>Loy, Brian A.</creatorcontrib><creatorcontrib>Yao, Chenglin</creatorcontrib><creatorcontrib>Nugent, Ben</creatorcontrib><creatorcontrib>Buchan, Zachary</creatorcontrib><creatorcontrib>Daeuble, John F.</creatorcontrib><creatorcontrib>Heemstra, Ron</creatorcontrib><creatorcontrib>Jones, David M.</creatorcontrib><creatorcontrib>Wilmot, Jeremy</creatorcontrib><creatorcontrib>Lu, Yu</creatorcontrib><creatorcontrib>DeKorver, Kyle</creatorcontrib><creatorcontrib>DeLorbe, Johnathan</creatorcontrib><creatorcontrib>Rigoli, Jared</creatorcontrib><title>Discovery of florylpicoxamid, a mimic of a macrocyclic natural product</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>[Display omitted]
Natural products have routinely been used both as sources of and inspiration for new crop protection active ingredients. The natural product UK-2A has potent anti-fungal activity but lacks key attributes for field translation. Post-fermentation conversion of UK-2A to fenpicoxamid resulted in an active ingredient with a new target site of action for cereal and banana pathogens. Here we demonstrate the creation of a synthetic variant of fenpicoxamid via identification of the structural elements of UK-2A that are needed for anti-fungal activity. Florylpicoxamid is a non-macrocyclic active ingredient bearing two fewer stereocenters than fenpicoxamid, controls a broad spectrum of fungal diseases at low use rates and has a concise, scalable route which is aligned with green chemistry principles. The development of florylpicoxamid represents the first example of using a stepwise deconstruction of a macrocyclic natural product to design a fully synthetic crop protection active ingredient.</description><subject>Antifungal Agents - chemical synthesis</subject><subject>Antifungal Agents - chemistry</subject><subject>Antifungal Agents - pharmacology</subject><subject>Ascomycota - drug effects</subject><subject>Biological Products - chemical synthesis</subject><subject>Biological Products - chemistry</subject><subject>Biological Products - pharmacology</subject><subject>Crop protection</subject><subject>Disease control</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Discovery</subject><subject>Florylpicoxamid</subject><subject>Fungicide</subject><subject>Macrocyclic Compounds - chemical synthesis</subject><subject>Macrocyclic Compounds - chemistry</subject><subject>Macrocyclic Compounds - pharmacology</subject><subject>Microbial Sensitivity Tests</subject><subject>Molecular Structure</subject><subject>Natural product mimic</subject><subject>Structure-Activity Relationship</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE1PwzAMhiMEgjH4AVxQjxzoyEeTNuKE-JaQuMA5Sh1HytSuI2kR-_dkGnDkZMt-_dp-CDljdMEoU1fLRdvDglPOFoypSso9MmOVqkohNNsnM6pVU9JGqyNynNKSUsorzQ7JkahqWXMtZ-ThLiQYPjFuisEXvhviplsHGL5sH9xlYYs-9AG2vZxaiANsoMuFlR2naLtiHQc3wXhCDrztEp7-xDl5f7h_u30qX14fn29vXkoQUoyldYq6GrhvnRLIJQdk0mvn0TXgPG8q6hhVEmuH6KxvhQBX26YWVkNbVWJOLna-ee_HhGk0fb4fu86ucJiS4VKrjENzmaVsJ81HpxTRm3UMvY0bw6jZ4jNLk_GZLT6zw5dnzn_sp7ZH9zfxyysLrncCzE9-BowmQcAVoAsRYTRuCP_YfwNLgoEZ</recordid><startdate>20211115</startdate><enddate>20211115</enddate><creator>Meyer, Kevin G.</creator><creator>Bravo-Altamirano, Karla</creator><creator>Herrick, Jessica</creator><creator>Loy, Brian A.</creator><creator>Yao, Chenglin</creator><creator>Nugent, Ben</creator><creator>Buchan, Zachary</creator><creator>Daeuble, John F.</creator><creator>Heemstra, Ron</creator><creator>Jones, David M.</creator><creator>Wilmot, Jeremy</creator><creator>Lu, Yu</creator><creator>DeKorver, Kyle</creator><creator>DeLorbe, Johnathan</creator><creator>Rigoli, Jared</creator><general>Elsevier Ltd</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><orcidid>https://orcid.org/0000-0001-7751-5027</orcidid><orcidid>https://orcid.org/0000-0003-1235-3463</orcidid></search><sort><creationdate>20211115</creationdate><title>Discovery of florylpicoxamid, a mimic of a macrocyclic natural product</title><author>Meyer, Kevin G. ; Bravo-Altamirano, Karla ; Herrick, Jessica ; Loy, Brian A. ; Yao, Chenglin ; Nugent, Ben ; Buchan, Zachary ; Daeuble, John F. ; Heemstra, Ron ; Jones, David M. ; Wilmot, Jeremy ; Lu, Yu ; DeKorver, Kyle ; DeLorbe, Johnathan ; Rigoli, Jared</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-ad60d7c2fbd63e252ce15f9dfed8cdf2840d1065e7deedafb33cd7a873a9cb443</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antifungal Agents - chemical synthesis</topic><topic>Antifungal Agents - chemistry</topic><topic>Antifungal Agents - pharmacology</topic><topic>Ascomycota - drug effects</topic><topic>Biological Products - chemical synthesis</topic><topic>Biological Products - chemistry</topic><topic>Biological Products - pharmacology</topic><topic>Crop protection</topic><topic>Disease control</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Discovery</topic><topic>Florylpicoxamid</topic><topic>Fungicide</topic><topic>Macrocyclic Compounds - chemical synthesis</topic><topic>Macrocyclic Compounds - chemistry</topic><topic>Macrocyclic Compounds - pharmacology</topic><topic>Microbial Sensitivity Tests</topic><topic>Molecular Structure</topic><topic>Natural product mimic</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Meyer, Kevin G.</creatorcontrib><creatorcontrib>Bravo-Altamirano, Karla</creatorcontrib><creatorcontrib>Herrick, Jessica</creatorcontrib><creatorcontrib>Loy, Brian A.</creatorcontrib><creatorcontrib>Yao, Chenglin</creatorcontrib><creatorcontrib>Nugent, Ben</creatorcontrib><creatorcontrib>Buchan, Zachary</creatorcontrib><creatorcontrib>Daeuble, John F.</creatorcontrib><creatorcontrib>Heemstra, Ron</creatorcontrib><creatorcontrib>Jones, David M.</creatorcontrib><creatorcontrib>Wilmot, Jeremy</creatorcontrib><creatorcontrib>Lu, Yu</creatorcontrib><creatorcontrib>DeKorver, Kyle</creatorcontrib><creatorcontrib>DeLorbe, Johnathan</creatorcontrib><creatorcontrib>Rigoli, Jared</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>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meyer, Kevin G.</au><au>Bravo-Altamirano, Karla</au><au>Herrick, Jessica</au><au>Loy, Brian A.</au><au>Yao, Chenglin</au><au>Nugent, Ben</au><au>Buchan, Zachary</au><au>Daeuble, John F.</au><au>Heemstra, Ron</au><au>Jones, David M.</au><au>Wilmot, Jeremy</au><au>Lu, Yu</au><au>DeKorver, Kyle</au><au>DeLorbe, Johnathan</au><au>Rigoli, Jared</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery of florylpicoxamid, a mimic of a macrocyclic natural product</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2021-11-15</date><risdate>2021</risdate><volume>50</volume><spage>116455</spage><epage>116455</epage><pages>116455-116455</pages><artnum>116455</artnum><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>[Display omitted]
Natural products have routinely been used both as sources of and inspiration for new crop protection active ingredients. The natural product UK-2A has potent anti-fungal activity but lacks key attributes for field translation. Post-fermentation conversion of UK-2A to fenpicoxamid resulted in an active ingredient with a new target site of action for cereal and banana pathogens. Here we demonstrate the creation of a synthetic variant of fenpicoxamid via identification of the structural elements of UK-2A that are needed for anti-fungal activity. Florylpicoxamid is a non-macrocyclic active ingredient bearing two fewer stereocenters than fenpicoxamid, controls a broad spectrum of fungal diseases at low use rates and has a concise, scalable route which is aligned with green chemistry principles. The development of florylpicoxamid represents the first example of using a stepwise deconstruction of a macrocyclic natural product to design a fully synthetic crop protection active ingredient.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>34757295</pmid><doi>10.1016/j.bmc.2021.116455</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-7751-5027</orcidid><orcidid>https://orcid.org/0000-0003-1235-3463</orcidid></addata></record> |
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| ispartof | Bioorganic & medicinal chemistry, 2021-11, Vol.50, p.116455-116455, Article 116455 |
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| subjects | Antifungal Agents - chemical synthesis Antifungal Agents - chemistry Antifungal Agents - pharmacology Ascomycota - drug effects Biological Products - chemical synthesis Biological Products - chemistry Biological Products - pharmacology Crop protection Disease control Dose-Response Relationship, Drug Drug Discovery Florylpicoxamid Fungicide Macrocyclic Compounds - chemical synthesis Macrocyclic Compounds - chemistry Macrocyclic Compounds - pharmacology Microbial Sensitivity Tests Molecular Structure Natural product mimic Structure-Activity Relationship |
| title | Discovery of florylpicoxamid, a mimic of a macrocyclic natural product |
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