{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/39115"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/39115","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Studies of paclitaxel analogs modified in ring C","abstract":"The structurally novel diterpenoid paclitaxel (Taxol®), originally isolated from <i>Taxus brevifolia</i>, is one of the most promising new anticancer drugs. Its structural complexity and unique biological activity have provided the impetus for a number of structure-activity relationship (SAR) studies for the last twenty years, with the aim of developing analogs with improved bioactivity. Because of the absence of information on the structure-activity relationship of the C-6 position and the ring C skeleton of paclitaxel, it was goal of this research to synthesize paclitaxel analogs modified in ring C in order to evaluate the effects of these modifications on biological activity and to reveal the chemistry of paclitaxel. The inactivity of the C-6 methylene group towards chemical modifications has been overcome by the formation of a double bond at the C- 6 and C-7 positions. Modification of the C-6 position has been achieved for the first time and over 20 new paclitaxel analogs modified at both the C-6 and C-7 positions have been synthesized. Biological evaluation of these compounds reveal that the C-6 and C-7 positions do not play significant roles in the biological activity of paclitaxel, although the two deoxygenated paclitaxel analogs, 7-deoxy-6α-hydroxypaclitaxel and 7,lO-dideoxy-6ahydroxypaclitaxel, were found to be more active than paclitaxel. Modification of the ring C skeleton has been accomplished for the first time, and several new C-<i>nor</i>-paclitaxel analogs have been synthesized. Biological evaluation showed that these C-<i>nor</i>-paclitaxel analogs were less active than paclitaxel, indicating that the ring C skeleton plays a crucial role in the biological activity of paclitaxel. Biological evaluation also showed that all oxetane ring-opened paditaxel analogs were essentially inactive. These results indicate that changes in the size and conformation of ring C and the attached oxetane ring make a significant contribution to the activity of paclitaxel.","abstract_html":"The structurally novel diterpenoid paclitaxel (Taxol®), originally isolated from &lt;i&gt;Taxus brevifolia&lt;/i&gt;, is one of the most promising new anticancer drugs. Its structural complexity and unique biological activity have provided the impetus for a number of structure-activity relationship (SAR) studies for the last twenty years, with the aim of developing analogs with improved bioactivity. Because of the absence of information on the structure-activity relationship of the C-6 position and the ring C skeleton of paclitaxel, it was goal of this research to synthesize paclitaxel analogs modified in ring C in order to evaluate the effects of these modifications on biological activity and to reveal the chemistry of paclitaxel. The inactivity of the C-6 methylene group towards chemical modifications has been overcome by the formation of a double bond at the C- 6 and C-7 positions. Modification of the C-6 position has been achieved for the first time and over 20 new paclitaxel analogs modified at both the C-6 and C-7 positions have been synthesized. Biological evaluation of these compounds reveal that the C-6 and C-7 positions do not play significant roles in the biological activity of paclitaxel, although the two deoxygenated paclitaxel analogs, 7-deoxy-6α-hydroxypaclitaxel and 7,lO-dideoxy-6ahydroxypaclitaxel, were found to be more active than paclitaxel. Modification of the ring C skeleton has been accomplished for the first time, and several new C-&lt;i&gt;nor&lt;/i&gt;-paclitaxel analogs have been synthesized. Biological evaluation showed that these C-&lt;i&gt;nor&lt;/i&gt;-paclitaxel analogs were less active than paclitaxel, indicating that the ring C skeleton plays a crucial role in the biological activity of paclitaxel. Biological evaluation also showed that all oxetane ring-opened paditaxel analogs were essentially inactive. These results indicate that changes in the size and conformation of ring C and the attached oxetane ring make a significant contribution to the activity of paclitaxel.","abstract_has_math":false,"creators":["Liang, Xian"],"institution":"Virginia Tech","degree_name":"Ph. D.","degree_level":"doctoral","degree_discipline":"Chemistry","degree_department":"Chemistry","school":null,"contributors":[],"advisors":[],"committee_chairs":["Kingston, David G. I."],"committee_members":["Bell, Harold M.","Castagnoli, Neal Jr.","Hanson, Brian E.","Tanko, James M."],"year":1996,"date_issued":"1996-03-05","date_published":"1996-03-05","updated_at":"2026-07-22T22:18:53Z","subjects":["anticancer agent","pactilaxel","modification","ring C"],"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-08082007-161932"],"render_values":[{"text":"etd-08082007-161932","href":null,"code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/10919/39115","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Kingston, David G. 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Its structural complexity and unique biological activity have provided the impetus for a number of structure-activity relationship (SAR) studies for the last twenty years, with the aim of developing analogs with improved bioactivity. Because of the absence of information on the structure-activity relationship of the C-6 position and the ring C skeleton of paclitaxel, it was goal of this research to synthesize paclitaxel analogs modified in ring C in order to evaluate the effects of these modifications on biological activity and to reveal the chemistry of paclitaxel. The inactivity of the C-6 methylene group towards chemical modifications has been overcome by the formation of a double bond at the C- 6 and C-7 positions. Modification of the C-6 position has been achieved for the first time and over 20 new paclitaxel analogs modified at both the C-6 and C-7 positions have been synthesized. Biological evaluation of these compounds reveal that the C-6 and C-7 positions do not play significant roles in the biological activity of paclitaxel, although the two deoxygenated paclitaxel analogs, 7-deoxy-6α-hydroxypaclitaxel and 7,lO-dideoxy-6ahydroxypaclitaxel, were found to be more active than paclitaxel. Modification of the ring C skeleton has been accomplished for the first time, and several new C-<i>nor</i>-paclitaxel analogs have been synthesized. Biological evaluation showed that these C-<i>nor</i>-paclitaxel analogs were less active than paclitaxel, indicating that the ring C skeleton plays a crucial role in the biological activity of paclitaxel. Biological evaluation also showed that all oxetane ring-opened paditaxel analogs were essentially inactive. These results indicate that changes in the size and conformation of ring C and the attached oxetane ring make a significant contribution to the activity of paclitaxel."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph. D."]},{"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":["Studies of paclitaxel analogs modified in ring C"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Kingston, David G. I."],"dc:contributor.committeemember":["Bell, Harold M.","Castagnoli, Neal Jr.","Hanson, Brian E.","Tanko, James M."],"dc:contributor.department":["Chemistry"],"dc:creator":["Liang, Xian"],"dc:date.accessioned":["2014-03-14T21:17:36Z"],"dc:date.available":["2014-03-14T21:17:36Z","2007-08-08"],"dc:date.issued":["1996-03-05"],"dc:description.abstract":["The structurally novel diterpenoid paclitaxel (Taxol®), originally isolated from <i>Taxus brevifolia</i>, is one of the most promising new anticancer drugs. Its structural complexity and unique biological activity have provided the impetus for a number of structure-activity relationship (SAR) studies for the last twenty years, with the aim of developing analogs with improved bioactivity. Because of the absence of information on the structure-activity relationship of the C-6 position and the ring C skeleton of paclitaxel, it was goal of this research to synthesize paclitaxel analogs modified in ring C in order to evaluate the effects of these modifications on biological activity and to reveal the chemistry of paclitaxel. The inactivity of the C-6 methylene group towards chemical modifications has been overcome by the formation of a double bond at the C- 6 and C-7 positions. Modification of the C-6 position has been achieved for the first time and over 20 new paclitaxel analogs modified at both the C-6 and C-7 positions have been synthesized. Biological evaluation of these compounds reveal that the C-6 and C-7 positions do not play significant roles in the biological activity of paclitaxel, although the two deoxygenated paclitaxel analogs, 7-deoxy-6α-hydroxypaclitaxel and 7,lO-dideoxy-6ahydroxypaclitaxel, were found to be more active than paclitaxel. Modification of the ring C skeleton has been accomplished for the first time, and several new C-<i>nor</i>-paclitaxel analogs have been synthesized. Biological evaluation showed that these C-<i>nor</i>-paclitaxel analogs were less active than paclitaxel, indicating that the ring C skeleton plays a crucial role in the biological activity of paclitaxel. Biological evaluation also showed that all oxetane ring-opened paditaxel analogs were essentially inactive. These results indicate that changes in the size and conformation of ring C and the attached oxetane ring make a significant contribution to the activity of paclitaxel."],"dc:description.degree":["Ph. D."],"dc:format.medium":["BTD"],"dc:format.mimetype":["application/pdf"],"dc:identifier.other":["etd-08082007-161932"],"dc:identifier.uri":["http://hdl.handle.net/10919/39115"],"dc:language.iso":["en"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["anticancer agent","pactilaxel","modification","ring C"],"dc:title":["Studies of paclitaxel analogs modified in ring C"],"dc:type":["Dissertation"],"dc:type.dcmitype":["Text"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Ph. D."],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:18:53Z"}