{"id":{"repo_id":"wayne-thes","oai_identifier":"oai:digitalcommons.wayne.edu:oa_dissertations-2219"},"canonical_url":"https://search.dev.ndltd.org/etd/wayne-thes/oai:digitalcommons.wayne.edu:oa_dissertations-2219","repository":{"repo_id":"wayne-thes","name":"Wayne State University","base_url":"https://digitalcommons.wayne.edu/do/oai/"},"display":{"title":"Synthesis of 3'-deoxy- and 2',3'-dideoxy-4'-C-alkyl-D-nucleosides: potential antiviral agents","abstract":"Novel methodology for the synthesis of 3'-deoxy- and 2' ,3'-dideoxy-4' -C-alkyl nucleosides has been developed. The target nucleosides are of interest as potential antiviral agents. Crucial features addressed by the methodology are: the ability to synthesize nucleosides analogs with a variety on 4'-C-alkyl substituents; exceptional stereocontrol over the C4' stereogenic center; and a semi-convergent synthesis, allowing the late stage N-glycosylation of heterocyclic bases. Both 4'-C-alkyl substituent variety and control of the C4' stereocenter are addressed by introducing the alkyl substituents and establishing the stereogenic center in a cyclopentene precursor. These alkyl substituted cyclopentenes are prepared by carbonyl alkylation of a biocatalitically derived enantiopure cyclopentenone. Employing the appropriate alkyl nucleophile in the alkylation of the cyclopentenone allows the introduction of a variety of alkyl substituents with exceptional stereocontrol. The five carbons of the alkyl substituted cyclopentene are then exposed as the five continuous carbons of a 4 -alkyl ribose analog by oxidative olefin cleavage. The 4-alkyl ribose analogs prepared in the fashion described above were then used to glycosylate a variety of heterocyclic bases by a Vorbrüggen type coupling. Providing complete β-selectivity in the formation of the N-glycoside. Adjustment of the C5' oxidation level then gives the 3'-deoxy-4'-C-alkyl nucleoside analogs. Deoxygenation at C2' by the method of Robins gave the 2' ,3' -dideoxy-4'-C-alkyl nucleoside analogs. Examples of target molecules prepared in this study include: 3'-deoxy- and 2' ,3' -dideoxy-4'-C-methyl analogs of uracil, 5-methyluracil, 5-fluorouracil, cytidine, 5-fluorocytidine, adenine and inosine; as well as, 3'-deoxy- and 2' ,3'-dideoxy-5-methyl-4' -C-phenyluridine.","abstract_html":"Novel methodology for the synthesis of 3'-deoxy- and 2' ,3'-dideoxy-4' -C-alkyl nucleosides has been developed. The target nucleosides are of interest as potential antiviral agents. Crucial features addressed by the methodology are: the ability to synthesize nucleosides analogs with a variety on 4'-C-alkyl substituents; exceptional stereocontrol over the C4' stereogenic center; and a semi-convergent synthesis, allowing the late stage N-glycosylation of heterocyclic bases. Both 4'-C-alkyl substituent variety and control of the C4' stereocenter are addressed by introducing the alkyl substituents and establishing the stereogenic center in a cyclopentene precursor. These alkyl substituted cyclopentenes are prepared by carbonyl alkylation of a biocatalitically derived enantiopure cyclopentenone. Employing the appropriate alkyl nucleophile in the alkylation of the cyclopentenone allows the introduction of a variety of alkyl substituents with exceptional stereocontrol. The five carbons of the alkyl substituted cyclopentene are then exposed as the five continuous carbons of a 4 -alkyl ribose analog by oxidative olefin cleavage. The 4-alkyl ribose analogs prepared in the fashion described above were then used to glycosylate a variety of heterocyclic bases by a Vorbrüggen type coupling. Providing complete β-selectivity in the formation of the N-glycoside. Adjustment of the C5' oxidation level then gives the 3'-deoxy-4'-C-alkyl nucleoside analogs. Deoxygenation at C2' by the method of Robins gave the 2' ,3' -dideoxy-4'-C-alkyl nucleoside analogs. Examples of target molecules prepared in this study include: 3'-deoxy- and 2' ,3' -dideoxy-4'-C-methyl analogs of uracil, 5-methyluracil, 5-fluorouracil, cytidine, 5-fluorocytidine, adenine and inosine; as well as, 3'-deoxy- and 2' ,3'-dideoxy-5-methyl-4' -C-phenyluridine.","abstract_has_math":false,"creators":["Wells, Gregory William"],"institution":null,"degree_name":"Ph.D.","degree_level":"Open Access Dissertation","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Professor Carl R. Johnson"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":1998,"date_issued":"1998-01-01T08:00:00Z","date_published":"1998-01-01T08:00:00Z","updated_at":"2026-07-24T06:00:03Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.wayne.edu/oa_dissertations/1220","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Professor Carl R. Johnson"]},{"key":"dc:creator","label":"Author","values":["Wells, Gregory William"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2015-10-01T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Open Access Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.wayne.edu/oa_dissertations/1220"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Novel methodology for the synthesis of 3'-deoxy- and 2' ,3'-dideoxy-4' -C-alkyl nucleosides has been developed. The target nucleosides are of interest as potential antiviral agents. Crucial features addressed by the methodology are: the ability to synthesize nucleosides analogs with a variety on 4'-C-alkyl substituents; exceptional stereocontrol over the C4' stereogenic center; and a semi-convergent synthesis, allowing the late stage N-glycosylation of heterocyclic bases. Both 4'-C-alkyl substituent variety and control of the C4' stereocenter are addressed by introducing the alkyl substituents and establishing the stereogenic center in a cyclopentene precursor. These alkyl substituted cyclopentenes are prepared by carbonyl alkylation of a biocatalitically derived enantiopure cyclopentenone. Employing the appropriate alkyl nucleophile in the alkylation of the cyclopentenone allows the introduction of a variety of alkyl substituents with exceptional stereocontrol. The five carbons of the alkyl substituted cyclopentene are then exposed as the five continuous carbons of a 4 -alkyl ribose analog by oxidative olefin cleavage. The 4-alkyl ribose analogs prepared in the fashion described above were then used to glycosylate a variety of heterocyclic bases by a Vorbrüggen type coupling. Providing complete β-selectivity in the formation of the N-glycoside. Adjustment of the C5' oxidation level then gives the 3'-deoxy-4'-C-alkyl nucleoside analogs. Deoxygenation at C2' by the method of Robins gave the 2' ,3' -dideoxy-4'-C-alkyl nucleoside analogs. Examples of target molecules prepared in this study include: 3'-deoxy- and 2' ,3' -dideoxy-4'-C-methyl analogs of uracil, 5-methyluracil, 5-fluorouracil, cytidine, 5-fluorocytidine, adenine and inosine; as well as, 3'-deoxy- and 2' ,3'-dideoxy-5-methyl-4' -C-phenyluridine."]},{"key":"dc:title","label":"Title","values":["Synthesis of 3'-deoxy- and 2',3'-dideoxy-4'-C-alkyl-D-nucleosides: potential antiviral agents"]}]}],"canonical_facts":{"dc:contributor":["Professor Carl R. Johnson"],"dc:creator":["Wells, Gregory William"],"dc:date.available":["2015-10-01T07:00:00Z"],"dc:description.abstract":["Novel methodology for the synthesis of 3'-deoxy- and 2' ,3'-dideoxy-4' -C-alkyl nucleosides has been developed. The target nucleosides are of interest as potential antiviral agents. Crucial features addressed by the methodology are: the ability to synthesize nucleosides analogs with a variety on 4'-C-alkyl substituents; exceptional stereocontrol over the C4' stereogenic center; and a semi-convergent synthesis, allowing the late stage N-glycosylation of heterocyclic bases. Both 4'-C-alkyl substituent variety and control of the C4' stereocenter are addressed by introducing the alkyl substituents and establishing the stereogenic center in a cyclopentene precursor. These alkyl substituted cyclopentenes are prepared by carbonyl alkylation of a biocatalitically derived enantiopure cyclopentenone. Employing the appropriate alkyl nucleophile in the alkylation of the cyclopentenone allows the introduction of a variety of alkyl substituents with exceptional stereocontrol. The five carbons of the alkyl substituted cyclopentene are then exposed as the five continuous carbons of a 4 -alkyl ribose analog by oxidative olefin cleavage. The 4-alkyl ribose analogs prepared in the fashion described above were then used to glycosylate a variety of heterocyclic bases by a Vorbrüggen type coupling. Providing complete β-selectivity in the formation of the N-glycoside. Adjustment of the C5' oxidation level then gives the 3'-deoxy-4'-C-alkyl nucleoside analogs. Deoxygenation at C2' by the method of Robins gave the 2' ,3' -dideoxy-4'-C-alkyl nucleoside analogs. Examples of target molecules prepared in this study include: 3'-deoxy- and 2' ,3' -dideoxy-4'-C-methyl analogs of uracil, 5-methyluracil, 5-fluorouracil, cytidine, 5-fluorocytidine, adenine and inosine; as well as, 3'-deoxy- and 2' ,3'-dideoxy-5-methyl-4' -C-phenyluridine."],"dc:identifier":["https://digitalcommons.wayne.edu/oa_dissertations/1220"],"dc:title":["Synthesis of 3'-deoxy- and 2',3'-dideoxy-4'-C-alkyl-D-nucleosides: potential antiviral agents"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Open Access Dissertation"],"thesis:degree_name":["Ph.D."]},"updated_at":"2026-07-24T06:00:03Z"}