{"id":{"repo_id":"ku","oai_identifier":"oai:kuscholarworks.ku.edu:1808/39225"},"canonical_url":"https://search.dev.ndltd.org/etd/ku/oai:kuscholarworks.ku.edu:1808/39225","repository":{"repo_id":"ku","name":"University of Kansas","base_url":"https://kuscholarworks.ku.edu/server/oai/request"},"display":{"title":"Phosphate Tether-mediated Approaches for the Syntheses of Complex Polyols, Natural Products and Related Analogs","abstract":"The development of new synthetic strategies, allowing for efficient asymmetric syntheses of complex biologically active natural products, natural product analogs, and pharmaceutical agents is a long-standing goal for synthetic chemists. In particular, divergent strategies that allow the generation of multiple scaffolds from a single set of starting materials is crucial for analog production, which in turn, can enhance the quality of screening decks in early phase drug discovery. In this regard, the use of temporary tethering of two advanced intermediates has been a very powerful way in streamlining synthetic sequences by decreasing the entropic demand associated with the reactions and thus, allowing to overcome the difficulties associated with the intermolecular reaction with the same components","abstract_html":"The development of new synthetic strategies, allowing for efficient asymmetric syntheses of complex biologically active natural products, natural product analogs, and pharmaceutical agents is a long-standing goal for synthetic chemists. In particular, divergent strategies that allow the generation of multiple scaffolds from a single set of starting materials is crucial for analog production, which in turn, can enhance the quality of screening decks in early phase drug discovery. In this regard, the use of temporary tethering of two advanced intermediates has been a very powerful way in streamlining synthetic sequences by decreasing the entropic demand associated with the reactions and thus, allowing to overcome the difficulties associated with the intermolecular reaction with the same components","abstract_has_math":false,"creators":["Ganguly, Arghya"],"institution":"University of Kansas","degree_name":"Ph.D.","degree_level":null,"degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":[],"advisors":["Hanson, Paul R"],"committee_chairs":[],"committee_members":[],"year":2020,"date_issued":"2020-01-01","date_published":"2020-01-01","updated_at":"2026-07-24T02:44:44Z","subjects":[],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["https://www.proquest.com/LegacyDocView/DISSNUM/27740906"],"render_values":[{"text":"https://www.proquest.com/LegacyDocView/DISSNUM/27740906","href":"https://www.proquest.com/LegacyDocView/DISSNUM/27740906","code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/1808/39225","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Hanson, Paul R"]},{"key":"dc:creator","label":"Author","values":["Ganguly, Arghya"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-04-25T04:53:43Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2026-04-25T04:53:43Z"]},{"key":"dc:date.issued","label":"Date","values":["2020-01-01"]},{"key":"dc:publisher","label":"Institution","values":["University of Kansas"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["https://www.proquest.com/LegacyDocView/DISSNUM/27740906"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/1808/39225"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The development of new synthetic strategies, allowing for efficient asymmetric syntheses of complex biologically active natural products, natural product analogs, and pharmaceutical agents is a long-standing goal for synthetic chemists. In particular, divergent strategies that allow the generation of multiple scaffolds from a single set of starting materials is crucial for analog production, which in turn, can enhance the quality of screening decks in early phase drug discovery. In this regard, the use of temporary tethering of two advanced intermediates has been a very powerful way in streamlining synthetic sequences by decreasing the entropic demand associated with the reactions and thus, allowing to overcome the difficulties associated with the intermolecular reaction with the same components","Temporary tether-mediated processes continue to play a great role in the development of new synthetic methods and the synthesis of complex natural products. Throughout development, the scope of tether-mediated protocols has expanded, and several tethers have been extensively explored which include silicon, boron, phosphate, magnesium, aluminum, zinc, sulfur, selenium, ketals etc. The first chapter of this thesis is focused on the literature review on recent advances on the tether-mediated strategies with silicon and phosphate tether as well as extensive body of work using boron, aluminum, magnesium and zinc tether.","In chapter-2, we have reported iterative one-pot sequential strategy for the synthesis of chiral 1,3-skipped polyol using a phosphate tether-mediated approach. For allylic alkylation reactions, we have utilized hydride and different carbon nucleophiles to obtain the asymmetric subunits containing possessing three to six alcohols in good yields and diastereoselectivity. This strategy was further employed to streamline the asymmetric synthesis of polyol backbones of 13-desmethyl lyngbouilloside, an unnatural analog of anticancer natural product lyngbouilloside. The key reactions involved in our synthesis of acyclic polyol backbone of 13-desmethyl-lyngbouilloside include one-pot sequential RCM/CM/ chemoselective hydrogenation, regio- and diastereoselective cuprate addition followed by tether removal, Pd-catalyzed reductive allylic transposition, Roskamp homologation, pyran formation.","Chapter-3 outlines our synthetic studies towards the synthesis of Leustroducsin B, a potent colony-stimulating factor inducer, are reported. The synthetic strategy to this novel phosphorylated polyene-, polyol- and pyranone-containing natural product involves a ring-closing metathesis (RCM), oxymercuration/Jones oxidation, cross metathesis (CM) with a lactol-olefinic subunit, and 1,2 addition of the Li-enolate of EtOAc as the key steps for the installation of the “western segment” of this molecule. Further studies towards synthesis of the natural product are underway. Chapter 4 is a compilation of the supporting informations and experimental works carried out in this dissertation."]},{"key":"dc:title","label":"Title","values":["Phosphate Tether-mediated Approaches for the Syntheses of Complex Polyols, Natural Products and Related Analogs"]}]}],"canonical_facts":{"dc:contributor.advisor":["Hanson, Paul R"],"dc:creator":["Ganguly, Arghya"],"dc:date.accessioned":["2026-04-25T04:53:43Z"],"dc:date.available":["2026-04-25T04:53:43Z"],"dc:date.issued":["2020-01-01"],"dc:description.abstract":["The development of new synthetic strategies, allowing for efficient asymmetric syntheses of complex biologically active natural products, natural product analogs, and pharmaceutical agents is a long-standing goal for synthetic chemists. In particular, divergent strategies that allow the generation of multiple scaffolds from a single set of starting materials is crucial for analog production, which in turn, can enhance the quality of screening decks in early phase drug discovery. In this regard, the use of temporary tethering of two advanced intermediates has been a very powerful way in streamlining synthetic sequences by decreasing the entropic demand associated with the reactions and thus, allowing to overcome the difficulties associated with the intermolecular reaction with the same components","Temporary tether-mediated processes continue to play a great role in the development of new synthetic methods and the synthesis of complex natural products. Throughout development, the scope of tether-mediated protocols has expanded, and several tethers have been extensively explored which include silicon, boron, phosphate, magnesium, aluminum, zinc, sulfur, selenium, ketals etc. The first chapter of this thesis is focused on the literature review on recent advances on the tether-mediated strategies with silicon and phosphate tether as well as extensive body of work using boron, aluminum, magnesium and zinc tether.","In chapter-2, we have reported iterative one-pot sequential strategy for the synthesis of chiral 1,3-skipped polyol using a phosphate tether-mediated approach. For allylic alkylation reactions, we have utilized hydride and different carbon nucleophiles to obtain the asymmetric subunits containing possessing three to six alcohols in good yields and diastereoselectivity. This strategy was further employed to streamline the asymmetric synthesis of polyol backbones of 13-desmethyl lyngbouilloside, an unnatural analog of anticancer natural product lyngbouilloside. The key reactions involved in our synthesis of acyclic polyol backbone of 13-desmethyl-lyngbouilloside include one-pot sequential RCM/CM/ chemoselective hydrogenation, regio- and diastereoselective cuprate addition followed by tether removal, Pd-catalyzed reductive allylic transposition, Roskamp homologation, pyran formation.","Chapter-3 outlines our synthetic studies towards the synthesis of Leustroducsin B, a potent colony-stimulating factor inducer, are reported. The synthetic strategy to this novel phosphorylated polyene-, polyol- and pyranone-containing natural product involves a ring-closing metathesis (RCM), oxymercuration/Jones oxidation, cross metathesis (CM) with a lactol-olefinic subunit, and 1,2 addition of the Li-enolate of EtOAc as the key steps for the installation of the “western segment” of this molecule. Further studies towards synthesis of the natural product are underway. Chapter 4 is a compilation of the supporting informations and experimental works carried out in this dissertation."],"dc:identifier.other":["https://www.proquest.com/LegacyDocView/DISSNUM/27740906"],"dc:identifier.uri":["https://hdl.handle.net/1808/39225"],"dc:language.iso":["en"],"dc:publisher":["University of Kansas"],"dc:title":["Phosphate Tether-mediated Approaches for the Syntheses of Complex Polyols, Natural Products and Related Analogs"],"dc:type":["Dissertation"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_name":["Ph.D."]},"updated_at":"2026-07-24T02:44:44Z"}