{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/6618"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/6618","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Precursor-Directed Identification of Natural Product Scaffolds","abstract":"The rapid generation of natural product analogs is a fundamental challenge in both the optimization of medicinal potency and exploration of novel biological activity. Previous work with Streptomyces variabilis has demonstrated that natural products that incorporate non-enzymatic transformation can be exploited for the rapid generation of analogs. Herein we demonstrate a general methodology to use fluorinated or isotopically labeled substrates to identify natural product frameworks prone to non-enzymatic pathways. As proof of principle our precursor directed methodology was used in the study of discoipyrrole A formation, the guided isolation of a novel iminoquinone and the detection of a novel ammosamide analog via incorporation of a carbon-based nucleophile.","abstract_html":"The rapid generation of natural product analogs is a fundamental challenge in both the optimization of medicinal potency and exploration of novel biological activity. Previous work with Streptomyces variabilis has demonstrated that natural products that incorporate non-enzymatic transformation can be exploited for the rapid generation of analogs. Herein we demonstrate a general methodology to use fluorinated or isotopically labeled substrates to identify natural product frameworks prone to non-enzymatic pathways. As proof of principle our precursor directed methodology was used in the study of discoipyrrole A formation, the guided isolation of a novel iminoquinone and the detection of a novel ammosamide analog via incorporation of a carbon-based nucleophile.","abstract_has_math":false,"creators":["Brumley, David Anderson"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["MacMillan, John"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-06-03T19:57:19Z","date_published":"2019-06-03T19:57:19Z","updated_at":"2026-07-24T05:52:29Z","subjects":["Amides","Biological Products","Heterocyclic Compounds, 3-Ring","Pyrrolidinones","Quinones","Streptomyces"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1103324459"],"render_values":[{"text":"1103324459","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/6618","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["MacMillan, John"]},{"key":"dc:creator","label":"Author","values":["Brumley, David Anderson"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-06-03T19:57:19Z","2017-05","2017-04-17","May 2017","2019-06-03T19:57:20Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Amides","Biological Products","Heterocyclic Compounds, 3-Ring","Pyrrolidinones","Quinones","Streptomyces"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/6618","1103324459"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The rapid generation of natural product analogs is a fundamental challenge in both the optimization of medicinal potency and exploration of novel biological activity. Previous work with Streptomyces variabilis has demonstrated that natural products that incorporate non-enzymatic transformation can be exploited for the rapid generation of analogs. Herein we demonstrate a general methodology to use fluorinated or isotopically labeled substrates to identify natural product frameworks prone to non-enzymatic pathways. As proof of principle our precursor directed methodology was used in the study of discoipyrrole A formation, the guided isolation of a novel iminoquinone and the detection of a novel ammosamide analog via incorporation of a carbon-based nucleophile."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Precursor-Directed Identification of Natural Product Scaffolds"]}]}],"canonical_facts":{"dc:contributor":["MacMillan, John"],"dc:creator":["Brumley, David Anderson"],"dc:date":["2019-06-03T19:57:19Z","2017-05","2017-04-17","May 2017","2019-06-03T19:57:20Z"],"dc:description":["The rapid generation of natural product analogs is a fundamental challenge in both the optimization of medicinal potency and exploration of novel biological activity. Previous work with Streptomyces variabilis has demonstrated that natural products that incorporate non-enzymatic transformation can be exploited for the rapid generation of analogs. Herein we demonstrate a general methodology to use fluorinated or isotopically labeled substrates to identify natural product frameworks prone to non-enzymatic pathways. As proof of principle our precursor directed methodology was used in the study of discoipyrrole A formation, the guided isolation of a novel iminoquinone and the detection of a novel ammosamide analog via incorporation of a carbon-based nucleophile."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/6618","1103324459"],"dc:language":["en"],"dc:subject":["Amides","Biological Products","Heterocyclic Compounds, 3-Ring","Pyrrolidinones","Quinones","Streptomyces"],"dc:title":["Precursor-Directed Identification of Natural Product Scaffolds"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:29Z"}