{"id":{"repo_id":"auckland-ms","oai_identifier":"oai:researchspace.auckland.ac.nz:2292/26696"},"canonical_url":"https://search.dev.ndltd.org/etd/auckland-ms/oai:researchspace.auckland.ac.nz:2292/26696","repository":{"repo_id":"auckland-ms","name":"University of Auckland","base_url":"https://researchspace.auckland.ac.nz/server/oai/request"},"display":{"title":"Total Synthesis of the 2-Nitropyrrole Natural Product Heronapyrrole C","abstract":"This thesis describes the enantioselective total synthesis of the marine natural product heronapyrrole C (3). Heronapyrrole C was isolated from a Streptomyces sp. (CMB-M0423) from a shallow water sand sample collected off Heron Island (Australia) by Capon and co-workers. It belongs to the exceptionally rare family of nitropyrrole natural products, known examples of which are limited to the 3-nitropyrrole pyrrolomycin class of Streptomyces antibiotics. It is also one of the first documented examples of natural products bearing a 2-nitropyrrole functionality. Heronapyrroles A-C were found to display promising activity against the Gram-positive bacteria without cytotoxicity toward mammalian cell lines. Alkene 136 was initially identified as a key intermediate for the synthesis of heronapyrrole C. Two synthetic strategies were investigated in this work for construction of alkene 136. While strategy I using a transition metal catalysed coupling reaction of 137 and 138 failed to afford the desired alkene 136, the Julia-Kocienski olefination of aldehyde 186 and sulfone 187 afforded stereoisomeric mixtures of 136. The low efficiency encountered in preparation of sulfone 187 also limited further investigation of this strategy. A revised strategy was next developed, utilising key intermediate 255 for access to heronapyrrole C (3). Two key fragments, aldehyde 172 and sulfone 255 were synthesised using readily available starting materials. Aldehyde 172 was obtained from pyrrole 146 in 5 steps and sulfone 255 was prepared from geraniol 146 in 11 steps. Unification of the two fragments was achieved via a Julia- Kocienski olefination. The key alkene intermediate 255 was converted into epoxide 274 by Shi epoxidation. The construction of the bis-THF scaffold was achieved by successive double TES deprotection and epoxide opening cyclisation. N-Protection of the 2-nitropyrrole motif was key to the successful synthesis of heronapyrrole C. The BOM group was initially used, but could not be removed in the final step. A revised protecting group strategy using Boz group enabled the successful synthesis of heronapyrrole C (3). A more flexible unified synthetic strategy, designed for synthesis of all the heronapyrroles, was also investigated. The strategy hinged on convergent synthesis of the key intermediate, alkene 294, by a vinylation of iodide 299 with a suitable vinyl organometallic species (300). The iodide coupling partner 299 was successfully synthesised from 2-nitropyrrole 144. A successful model reaction between iodide 299 and vinyltributyltin indicated the viability of the vinylation strategy, however, the synthesis of coupling partner 300 needs further investigation.","abstract_html":"This thesis describes the enantioselective total synthesis of the marine natural product heronapyrrole C (3). Heronapyrrole C was isolated from a Streptomyces sp. (CMB-M0423) from a shallow water sand sample collected off Heron Island (Australia) by Capon and co-workers. It belongs to the exceptionally rare family of nitropyrrole natural products, known examples of which are limited to the 3-nitropyrrole pyrrolomycin class of Streptomyces antibiotics. It is also one of the first documented examples of natural products bearing a 2-nitropyrrole functionality. Heronapyrroles A-C were found to display promising activity against the Gram-positive bacteria without cytotoxicity toward mammalian cell lines. Alkene 136 was initially identified as a key intermediate for the synthesis of heronapyrrole C. Two synthetic strategies were investigated in this work for construction of alkene 136. While strategy I using a transition metal catalysed coupling reaction of 137 and 138 failed to afford the desired alkene 136, the Julia-Kocienski olefination of aldehyde 186 and sulfone 187 afforded stereoisomeric mixtures of 136. The low efficiency encountered in preparation of sulfone 187 also limited further investigation of this strategy. A revised strategy was next developed, utilising key intermediate 255 for access to heronapyrrole C (3). Two key fragments, aldehyde 172 and sulfone 255 were synthesised using readily available starting materials. Aldehyde 172 was obtained from pyrrole 146 in 5 steps and sulfone 255 was prepared from geraniol 146 in 11 steps. Unification of the two fragments was achieved via a Julia- Kocienski olefination. The key alkene intermediate 255 was converted into epoxide 274 by Shi epoxidation. The construction of the bis-THF scaffold was achieved by successive double TES deprotection and epoxide opening cyclisation. N-Protection of the 2-nitropyrrole motif was key to the successful synthesis of heronapyrrole C. The BOM group was initially used, but could not be removed in the final step. A revised protecting group strategy using Boz group enabled the successful synthesis of heronapyrrole C (3). A more flexible unified synthetic strategy, designed for synthesis of all the heronapyrroles, was also investigated. The strategy hinged on convergent synthesis of the key intermediate, alkene 294, by a vinylation of iodide 299 with a suitable vinyl organometallic species (300). The iodide coupling partner 299 was successfully synthesised from 2-nitropyrrole 144. A successful model reaction between iodide 299 and vinyltributyltin indicated the viability of the vinylation strategy, however, the synthesis of coupling partner 300 needs further investigation.","abstract_has_math":false,"creators":["Ding, Xiaobo"],"institution":"ResearchSpace@Auckland","degree_name":"PhD","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Brimble, M"],"committee_chairs":[],"committee_members":[],"year":2015,"date_issued":"2015","date_published":"2015","updated_at":"2026-07-24T01:05:11Z","subjects":[],"languages":[],"rights":["Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher."],"rights_urls":["https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm"],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/2292/26696","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Brimble, M"]},{"key":"dc:creator","label":"Author","values":["Ding, Xiaobo"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2015-08-13T02:31:04Z"]},{"key":"dc:date.issued","label":"Date","values":["2015"]},{"key":"dc:publisher","label":"Institution","values":["ResearchSpace@Auckland"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["PhD"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Auckland"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:rights","label":"Dc Rights","values":["Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. 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It is also one of the first documented examples of natural products bearing a 2-nitropyrrole functionality. Heronapyrroles A-C were found to display promising activity against the Gram-positive bacteria without cytotoxicity toward mammalian cell lines. Alkene 136 was initially identified as a key intermediate for the synthesis of heronapyrrole C. Two synthetic strategies were investigated in this work for construction of alkene 136. While strategy I using a transition metal catalysed coupling reaction of 137 and 138 failed to afford the desired alkene 136, the Julia-Kocienski olefination of aldehyde 186 and sulfone 187 afforded stereoisomeric mixtures of 136. The low efficiency encountered in preparation of sulfone 187 also limited further investigation of this strategy. A revised strategy was next developed, utilising key intermediate 255 for access to heronapyrrole C (3). Two key fragments, aldehyde 172 and sulfone 255 were synthesised using readily available starting materials. Aldehyde 172 was obtained from pyrrole 146 in 5 steps and sulfone 255 was prepared from geraniol 146 in 11 steps. Unification of the two fragments was achieved via a Julia- Kocienski olefination. The key alkene intermediate 255 was converted into epoxide 274 by Shi epoxidation. The construction of the bis-THF scaffold was achieved by successive double TES deprotection and epoxide opening cyclisation. N-Protection of the 2-nitropyrrole motif was key to the successful synthesis of heronapyrrole C. The BOM group was initially used, but could not be removed in the final step. A revised protecting group strategy using Boz group enabled the successful synthesis of heronapyrrole C (3). A more flexible unified synthetic strategy, designed for synthesis of all the heronapyrroles, was also investigated. The strategy hinged on convergent synthesis of the key intermediate, alkene 294, by a vinylation of iodide 299 with a suitable vinyl organometallic species (300). The iodide coupling partner 299 was successfully synthesised from 2-nitropyrrole 144. A successful model reaction between iodide 299 and vinyltributyltin indicated the viability of the vinylation strategy, however, the synthesis of coupling partner 300 needs further investigation."]},{"key":"dc:title","label":"Title","values":["Total Synthesis of the 2-Nitropyrrole Natural Product Heronapyrrole C"]}]}],"canonical_facts":{"dc:contributor.advisor":["Brimble, M"],"dc:creator":["Ding, Xiaobo"],"dc:date.accessioned":["2015-08-13T02:31:04Z"],"dc:date.issued":["2015"],"dc:description.abstract":["This thesis describes the enantioselective total synthesis of the marine natural product heronapyrrole C (3). Heronapyrrole C was isolated from a Streptomyces sp. (CMB-M0423) from a shallow water sand sample collected off Heron Island (Australia) by Capon and co-workers. It belongs to the exceptionally rare family of nitropyrrole natural products, known examples of which are limited to the 3-nitropyrrole pyrrolomycin class of Streptomyces antibiotics. It is also one of the first documented examples of natural products bearing a 2-nitropyrrole functionality. Heronapyrroles A-C were found to display promising activity against the Gram-positive bacteria without cytotoxicity toward mammalian cell lines. Alkene 136 was initially identified as a key intermediate for the synthesis of heronapyrrole C. Two synthetic strategies were investigated in this work for construction of alkene 136. While strategy I using a transition metal catalysed coupling reaction of 137 and 138 failed to afford the desired alkene 136, the Julia-Kocienski olefination of aldehyde 186 and sulfone 187 afforded stereoisomeric mixtures of 136. The low efficiency encountered in preparation of sulfone 187 also limited further investigation of this strategy. A revised strategy was next developed, utilising key intermediate 255 for access to heronapyrrole C (3). Two key fragments, aldehyde 172 and sulfone 255 were synthesised using readily available starting materials. Aldehyde 172 was obtained from pyrrole 146 in 5 steps and sulfone 255 was prepared from geraniol 146 in 11 steps. Unification of the two fragments was achieved via a Julia- Kocienski olefination. The key alkene intermediate 255 was converted into epoxide 274 by Shi epoxidation. The construction of the bis-THF scaffold was achieved by successive double TES deprotection and epoxide opening cyclisation. N-Protection of the 2-nitropyrrole motif was key to the successful synthesis of heronapyrrole C. The BOM group was initially used, but could not be removed in the final step. A revised protecting group strategy using Boz group enabled the successful synthesis of heronapyrrole C (3). A more flexible unified synthetic strategy, designed for synthesis of all the heronapyrroles, was also investigated. The strategy hinged on convergent synthesis of the key intermediate, alkene 294, by a vinylation of iodide 299 with a suitable vinyl organometallic species (300). The iodide coupling partner 299 was successfully synthesised from 2-nitropyrrole 144. A successful model reaction between iodide 299 and vinyltributyltin indicated the viability of the vinylation strategy, however, the synthesis of coupling partner 300 needs further investigation."],"dc:identifier.uri":["https://hdl.handle.net/2292/26696"],"dc:publisher":["ResearchSpace@Auckland"],"dc:rights":["Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher."],"dc:rights.uri":["https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm"],"dc:title":["Total Synthesis of the 2-Nitropyrrole Natural Product Heronapyrrole C"],"dc:type":["Thesis"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["PhD"],"thesis:institution_name":["The University of Auckland"]},"updated_at":"2026-07-24T01:05:11Z"}