{"id":{"repo_id":"penn","oai_identifier":"oai:repository.upenn.edu:20.500.14332/27922"},"canonical_url":"https://search.dev.ndltd.org/etd/penn/oai:repository.upenn.edu:20.500.14332/27922","repository":{"repo_id":"penn","name":"University of Pennsylvania","base_url":"https://repository.upenn.edu/server/oai/request"},"display":{"title":"Towards the Total Synthesis of Spirastrellolide E: Investigations into Advanced Southern Hemisphere Fragments","abstract":"This dissertation describes progress towards the synthesis of spirastrellolide E, a potent cytotoxic marine macrolide. In particular, the synthesis of advanced southern hemisphere fragments is reported. Chapter 1 details the isolation, structural determination, and biological activity of the spirastrellolide family, as well as synthetic efforts towards members of the family. Chapter 2 describes the evolution of the Smith group synthetic strategy towards the spirastrellolides, details the choice of target for a total synthesis effort, and describes a successful first generation approach to a relevant advanced southern hemisphere fragment. Key steps involve a convergent Type I Anion Relay Chemistry (ARC) union and a gold catalyzed directed spiroketalization. Chapter 3 then revises the overall retrosynthetic analysis by proposing a novel strategy for hemisphere union, involving a cross metathesis/epoxidation/epoxide ring opening cascade, and describes the synthesis of more than 500 mg of a revised southern hemisphere fragment. In addition, the mechanism of the key directed gold catalyzed spiroketalization is discussed in detail. A stereochemical rationale for diverging outcomes during spiroketalization is described.","abstract_html":"This dissertation describes progress towards the synthesis of spirastrellolide E, a potent cytotoxic marine macrolide. In particular, the synthesis of advanced southern hemisphere fragments is reported. Chapter 1 details the isolation, structural determination, and biological activity of the spirastrellolide family, as well as synthetic efforts towards members of the family. Chapter 2 describes the evolution of the Smith group synthetic strategy towards the spirastrellolides, details the choice of target for a total synthesis effort, and describes a successful first generation approach to a relevant advanced southern hemisphere fragment. Key steps involve a convergent Type I Anion Relay Chemistry (ARC) union and a gold catalyzed directed spiroketalization. Chapter 3 then revises the overall retrosynthetic analysis by proposing a novel strategy for hemisphere union, involving a cross metathesis/epoxidation/epoxide ring opening cascade, and describes the synthesis of more than 500 mg of a revised southern hemisphere fragment. In addition, the mechanism of the key directed gold catalyzed spiroketalization is discussed in detail. A stereochemical rationale for diverging outcomes during spiroketalization is described.","abstract_has_math":false,"creators":["Sokolsky, Alexander"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Amos B. Smith"],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015-01-01","date_published":"2015-01-01","updated_at":"2026-07-24T03:47:06Z","subjects":[],"languages":["en"],"rights":["Alexander Sokolsky"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://repository.upenn.edu/handle/20.500.14332/27922","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Amos B. 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In particular, the synthesis of advanced southern hemisphere fragments is reported. Chapter 1 details the isolation, structural determination, and biological activity of the spirastrellolide family, as well as synthetic efforts towards members of the family. Chapter 2 describes the evolution of the Smith group synthetic strategy towards the spirastrellolides, details the choice of target for a total synthesis effort, and describes a successful first generation approach to a relevant advanced southern hemisphere fragment. Key steps involve a convergent Type I Anion Relay Chemistry (ARC) union and a gold catalyzed directed spiroketalization. Chapter 3 then revises the overall retrosynthetic analysis by proposing a novel strategy for hemisphere union, involving a cross metathesis/epoxidation/epoxide ring opening cascade, and describes the synthesis of more than 500 mg of a revised southern hemisphere fragment. In addition, the mechanism of the key directed gold catalyzed spiroketalization is discussed in detail. A stereochemical rationale for diverging outcomes during spiroketalization is described."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Doctor of Philosophy (PhD)"]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Towards the Total Synthesis of Spirastrellolide E: Investigations into Advanced Southern Hemisphere Fragments"]}]}],"canonical_facts":{"dc:contributor.advisor":["Amos B. Smith"],"dc:creator":["Sokolsky, Alexander"],"dc:date":["2023-05-17T12:00:44.000"],"dc:date.accessioned":["2023-05-22T16:25:18Z"],"dc:date.available":["2001-01-01T00:00:00Z"],"dc:date.issued":["2015-01-01"],"dc:description.abstract":["This dissertation describes progress towards the synthesis of spirastrellolide E, a potent cytotoxic marine macrolide. In particular, the synthesis of advanced southern hemisphere fragments is reported. Chapter 1 details the isolation, structural determination, and biological activity of the spirastrellolide family, as well as synthetic efforts towards members of the family. Chapter 2 describes the evolution of the Smith group synthetic strategy towards the spirastrellolides, details the choice of target for a total synthesis effort, and describes a successful first generation approach to a relevant advanced southern hemisphere fragment. Key steps involve a convergent Type I Anion Relay Chemistry (ARC) union and a gold catalyzed directed spiroketalization. Chapter 3 then revises the overall retrosynthetic analysis by proposing a novel strategy for hemisphere union, involving a cross metathesis/epoxidation/epoxide ring opening cascade, and describes the synthesis of more than 500 mg of a revised southern hemisphere fragment. In addition, the mechanism of the key directed gold catalyzed spiroketalization is discussed in detail. A stereochemical rationale for diverging outcomes during spiroketalization is described."],"dc:description.degree":["Doctor of Philosophy (PhD)"],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["https://repository.upenn.edu/handle/20.500.14332/27922"],"dc:language":["en"],"dc:rights":["Alexander Sokolsky"],"dc:title":["Towards the Total Synthesis of Spirastrellolide E: Investigations into Advanced Southern Hemisphere Fragments"],"dc:type":["Dissertation/Thesis"]},"updated_at":"2026-07-24T03:47:06Z"}