{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/104826"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/104826","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Synthesis of sesquiterpene-tropolones","abstract":"A modular synthetic platform for the synthesis of the multi-bioactive sesquiterpene-tropolone natural products has been developed in an effort to provide general synthetic access to this class of compounds and related structures. In this work, the convergence of the sesquiterpene and tropolone fragments is enabled by a hetero-Diels–Alder reaction between a tropolone ortho-quinone methide and derivatives of α–humulene. Concise and scalable syntheses of both fragments are described, as well as alternative approaches to key intermediates. During the development of the tropolone synthesis, an unprecedented photochemical fragmentation was discovered. Two natural products, epolone B and deoxypycnidione have been synthesized employing this strategy, as well as two diastereomers of pycnidione. In these studies, a correction to the originally reported structure of epolone B is suggested based upon X-ray crystallographic data. The synthetic compounds were found to be cytotoxic to A459 and HCT116 cell lines. Current efforts are focused on synthesizing pycnidione in its correct relative stereochemical configuration. Future directions include application of these fragments in hetero-Diels–Alder reactions to synthesize related sesquiterpene-tropolones, other tropolone containing natural products, and bistropolone congeners for biological evaluation.","abstract_html":"A modular synthetic platform for the synthesis of the multi-bioactive sesquiterpene-tropolone natural products has been developed in an effort to provide general synthetic access to this class of compounds and related structures. In this work, the convergence of the sesquiterpene and tropolone fragments is enabled by a hetero-Diels–Alder reaction between a tropolone ortho-quinone methide and derivatives of α–humulene. Concise and scalable syntheses of both fragments are described, as well as alternative approaches to key intermediates. During the development of the tropolone synthesis, an unprecedented photochemical fragmentation was discovered. Two natural products, epolone B and deoxypycnidione have been synthesized employing this strategy, as well as two diastereomers of pycnidione. In these studies, a correction to the originally reported structure of epolone B is suggested based upon X-ray crystallographic data. The synthetic compounds were found to be cytotoxic to A459 and HCT116 cell lines. Current efforts are focused on synthesizing pycnidione in its correct relative stereochemical configuration. Future directions include application of these fragments in hetero-Diels–Alder reactions to synthesize related sesquiterpene-tropolones, other tropolone containing natural products, and bistropolone congeners for biological evaluation.","abstract_has_math":false,"creators":["Bemis, Christopher Yngwie"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Sarlah, David","Denmark, Scott E.","Hergenrother, Paul J.","Silverman, Scott K."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-08-23T19:51:52Z","date_published":"2019-08-23T19:51:52Z","updated_at":"2026-07-22T22:24:42Z","subjects":["total synthesis","organic synthesis","sesquiterpene-tropolones","meroterpenoids","tropolone","pycnidione","epolone A","epolone B","eupenifeldin"],"languages":["en"],"rights":["Copyright 2019 Christopher Bemis"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/104826","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Sarlah, David","Denmark, Scott E.","Hergenrother, Paul J.","Silverman, Scott K."]},{"key":"dc:creator","label":"Author","values":["Bemis, Christopher Yngwie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-08-23T19:51:52Z","2019-04-15","2019-05"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["total synthesis","organic synthesis","sesquiterpene-tropolones","meroterpenoids","tropolone","pycnidione","epolone A","epolone B","eupenifeldin"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2019 Christopher Bemis"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/104826"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["A modular synthetic platform for the synthesis of the multi-bioactive sesquiterpene-tropolone natural products has been developed in an effort to provide general synthetic access to this class of compounds and related structures. In this work, the convergence of the sesquiterpene and tropolone fragments is enabled by a hetero-Diels–Alder reaction between a tropolone ortho-quinone methide and derivatives of α–humulene. Concise and scalable syntheses of both fragments are described, as well as alternative approaches to key intermediates. During the development of the tropolone synthesis, an unprecedented photochemical fragmentation was discovered. Two natural products, epolone B and deoxypycnidione have been synthesized employing this strategy, as well as two diastereomers of pycnidione. In these studies, a correction to the originally reported structure of epolone B is suggested based upon X-ray crystallographic data. The synthetic compounds were found to be cytotoxic to A459 and HCT116 cell lines. Current efforts are focused on synthesizing pycnidione in its correct relative stereochemical configuration. Future directions include application of these fragments in hetero-Diels–Alder reactions to synthesize related sesquiterpene-tropolones, other tropolone containing natural products, and bistropolone congeners for biological evaluation.","Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2019-08-22 without embargo terms","The student, Christopher Bemis, accepted the attached license on 2019-04-15 at 08:45.","The student, Christopher Bemis, submitted this Dissertation for approval on 2019-04-15 at 08:54.","This Dissertation was approved for publication on 2019-04-15 at 15:02.","DSpace SAF Submission Ingestion Package generated from Vireo submission #13619 on 2019-08-22 at 14:43:27","Made available in DSpace on 2019-08-23T19:51:52Z (GMT). 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In this work, the convergence of the sesquiterpene and tropolone fragments is enabled by a hetero-Diels–Alder reaction between a tropolone ortho-quinone methide and derivatives of α–humulene. Concise and scalable syntheses of both fragments are described, as well as alternative approaches to key intermediates. During the development of the tropolone synthesis, an unprecedented photochemical fragmentation was discovered. Two natural products, epolone B and deoxypycnidione have been synthesized employing this strategy, as well as two diastereomers of pycnidione. In these studies, a correction to the originally reported structure of epolone B is suggested based upon X-ray crystallographic data. The synthetic compounds were found to be cytotoxic to A459 and HCT116 cell lines. Current efforts are focused on synthesizing pycnidione in its correct relative stereochemical configuration. Future directions include application of these fragments in hetero-Diels–Alder reactions to synthesize related sesquiterpene-tropolones, other tropolone containing natural products, and bistropolone congeners for biological evaluation.","Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2019-08-22 without embargo terms","The student, Christopher Bemis, accepted the attached license on 2019-04-15 at 08:45.","The student, Christopher Bemis, submitted this Dissertation for approval on 2019-04-15 at 08:54.","This Dissertation was approved for publication on 2019-04-15 at 15:02.","DSpace SAF Submission Ingestion Package generated from Vireo submission #13619 on 2019-08-22 at 14:43:27","Made available in DSpace on 2019-08-23T19:51:52Z (GMT). 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