{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/44945"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/44945","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Enediynylacridans: design and synthesis of oxidase triggered diyl progenitors","abstract":"In 1972, Bergman reported cycloaromatization via 1,4- benzenoid diradicals of enediyne systems. Since 1985, five enediyne fungal products with anticancer antibiotic activity have been structurally elucidated, namely, neocarzinostatin chromophore, the calicheamicins, the esperamicins, the dynemicins, and kedarcidin chromophore. These compounds are delivered to DNA by a targeting mechanism and upon activation undergo a series of reactions which results in the generation of radicals via Bergman or Myers cyclization. Myers cyclization is aromatization of certain enynylallenes to Q,3-dehydro toluene diradicals. These radicals then abstract hydrogen atoms from DNA resulting in strand cleavage. The goal of my research project is the synthesis of enediynylacridans s~ch as 3,6-bisdimethylamino-9-[3-(2- ethynylphenyl)prop-2-ynyl]acridan which potentially have the same type of anticancer antibiotic activity as the natural products. Oxidation of the acridan (dihydro acridine) to the acridine would induce base catalyzed propargyl-allenyl isomerization. This would serve as the triggering device which leads to Myers cyclization and thus the diradical. The acridine portion of the molecule would also serve as the delivery system, as acridines are known to interact with DNA via intercalation. There is also interest in determining to what extent an N-oxide functionality would accelerate the Myers cyclization due to the incipient nitroxide radical. Another area of interest involves chemical oxidation of the acridans to the acridines.","abstract_html":"In 1972, Bergman reported cycloaromatization via 1,4- benzenoid diradicals of enediyne systems. Since 1985, five enediyne fungal products with anticancer antibiotic activity have been structurally elucidated, namely, neocarzinostatin chromophore, the calicheamicins, the esperamicins, the dynemicins, and kedarcidin chromophore. These compounds are delivered to DNA by a targeting mechanism and upon activation undergo a series of reactions which results in the generation of radicals via Bergman or Myers cyclization. Myers cyclization is aromatization of certain enynylallenes to Q,3-dehydro toluene diradicals. These radicals then abstract hydrogen atoms from DNA resulting in strand cleavage. The goal of my research project is the synthesis of enediynylacridans s~ch as 3,6-bisdimethylamino-9-[3-(2- ethynylphenyl)prop-2-ynyl]acridan which potentially have the same type of anticancer antibiotic activity as the natural products. Oxidation of the acridan (dihydro acridine) to the acridine would induce base catalyzed propargyl-allenyl isomerization. This would serve as the triggering device which leads to Myers cyclization and thus the diradical. The acridine portion of the molecule would also serve as the delivery system, as acridines are known to interact with DNA via intercalation. There is also interest in determining to what extent an N-oxide functionality would accelerate the Myers cyclization due to the incipient nitroxide radical. Another area of interest involves chemical oxidation of the acridans to the acridines.","abstract_has_math":false,"creators":["Greenwood, Stacey Noelle"],"institution":"Virginia Tech","degree_name":"Master of Science","degree_level":"masters","degree_discipline":"Chemistry","degree_department":"Chemistry","school":null,"contributors":[],"advisors":[],"committee_chairs":["Becker, David A."],"committee_members":["Merola, Joseph S.","Tanko, James M.","White, Robert H."],"year":1993,"date_issued":"1993-07-05","date_published":"1993-07-05","updated_at":"2026-07-22T22:19:31Z","subjects":[],"languages":["en"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-09292009-020332"],"render_values":[{"text":"etd-09292009-020332","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10919/44945","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Becker, David A."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Merola, Joseph S.","Tanko, James M.","White, Robert H."]},{"key":"dc:contributor.department","label":"Department","values":["Chemistry"]},{"key":"dc:creator","label":"Author","values":["Greenwood, Stacey Noelle"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2014-03-14T21:46:38Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2014-03-14T21:46:38Z","2009-09-29"]},{"key":"dc:date.issued","label":"Date","values":["1993-07-05"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.dcmitype","label":"Dc Type Dcmitype","values":["Text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["masters"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Virginia Polytechnic Institute and State University"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["etd-09292009-020332"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10919/44945"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["In 1972, Bergman reported cycloaromatization via 1,4- benzenoid diradicals of enediyne systems. Since 1985, five enediyne fungal products with anticancer antibiotic activity have been structurally elucidated, namely, neocarzinostatin chromophore, the calicheamicins, the esperamicins, the dynemicins, and kedarcidin chromophore. These compounds are delivered to DNA by a targeting mechanism and upon activation undergo a series of reactions which results in the generation of radicals via Bergman or Myers cyclization. Myers cyclization is aromatization of certain enynylallenes to Q,3-dehydro toluene diradicals. These radicals then abstract hydrogen atoms from DNA resulting in strand cleavage. The goal of my research project is the synthesis of enediynylacridans s~ch as 3,6-bisdimethylamino-9-[3-(2- ethynylphenyl)prop-2-ynyl]acridan which potentially have the same type of anticancer antibiotic activity as the natural products. Oxidation of the acridan (dihydro acridine) to the acridine would induce base catalyzed propargyl-allenyl isomerization. This would serve as the triggering device which leads to Myers cyclization and thus the diradical. The acridine portion of the molecule would also serve as the delivery system, as acridines are known to interact with DNA via intercalation. There is also interest in determining to what extent an N-oxide functionality would accelerate the Myers cyclization due to the incipient nitroxide radical. Another area of interest involves chemical oxidation of the acridans to the acridines."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Master of Science"]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["BTD"]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Enediynylacridans: design and synthesis of oxidase triggered diyl progenitors"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Becker, David A."],"dc:contributor.committeemember":["Merola, Joseph S.","Tanko, James M.","White, Robert H."],"dc:contributor.department":["Chemistry"],"dc:creator":["Greenwood, Stacey Noelle"],"dc:date.accessioned":["2014-03-14T21:46:38Z"],"dc:date.available":["2014-03-14T21:46:38Z","2009-09-29"],"dc:date.issued":["1993-07-05"],"dc:description.abstract":["In 1972, Bergman reported cycloaromatization via 1,4- benzenoid diradicals of enediyne systems. Since 1985, five enediyne fungal products with anticancer antibiotic activity have been structurally elucidated, namely, neocarzinostatin chromophore, the calicheamicins, the esperamicins, the dynemicins, and kedarcidin chromophore. These compounds are delivered to DNA by a targeting mechanism and upon activation undergo a series of reactions which results in the generation of radicals via Bergman or Myers cyclization. Myers cyclization is aromatization of certain enynylallenes to Q,3-dehydro toluene diradicals. These radicals then abstract hydrogen atoms from DNA resulting in strand cleavage. The goal of my research project is the synthesis of enediynylacridans s~ch as 3,6-bisdimethylamino-9-[3-(2- ethynylphenyl)prop-2-ynyl]acridan which potentially have the same type of anticancer antibiotic activity as the natural products. Oxidation of the acridan (dihydro acridine) to the acridine would induce base catalyzed propargyl-allenyl isomerization. This would serve as the triggering device which leads to Myers cyclization and thus the diradical. The acridine portion of the molecule would also serve as the delivery system, as acridines are known to interact with DNA via intercalation. There is also interest in determining to what extent an N-oxide functionality would accelerate the Myers cyclization due to the incipient nitroxide radical. Another area of interest involves chemical oxidation of the acridans to the acridines."],"dc:description.degree":["Master of Science"],"dc:format.medium":["BTD"],"dc:format.mimetype":["application/pdf"],"dc:identifier.other":["etd-09292009-020332"],"dc:identifier.uri":["http://hdl.handle.net/10919/44945"],"dc:language.iso":["en"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:title":["Enediynylacridans: design and synthesis of oxidase triggered diyl progenitors"],"dc:type":["Thesis"],"dc:type.dcmitype":["Text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["masters"],"thesis:degree_name":["Master of Science"],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:19:31Z"}