Tubulysin is a natural product with potential anti-cancer activity. The two gamma-amino acids in the Tuv and Tup fragments of tubulysin were synthesized. Evans' oxazolidinone chemistry was employed for the stereoselective synthesis of Cbz-beta-homovaline in Tuv fragment. A crystal structure of the Tup fragment was obtained.
Cyclin dependent kinase 5 (CDK5) is one of the kinases that can hyperphosphorylate tau. Selective inhibition of the CDK5/p25 complex may be a useful component for Alzheimer's disease therapy. Benzimidazole based analogs of the known non-selective CDK5 inhibitor (R)-Roscovitine were designed. Synthesis of 6-benzyl substituted benzimidazole analogs was developed and two compounds were synthesized in this series. Two methods of the synthesis of 6-(2-hydroxy-1-alkyl)amino substituted benzimidazole analogs were developed.","abstract_html":"This thesis describes the design and synthesis of 1,4,6-trisubstituted benzimidazoles as CDK5 inhibitors and the progress toward the total synthesis of tubulysin D.</p><p> Tubulysin is a natural product with potential anti-cancer activity. The two gamma-amino acids in the Tuv and Tup fragments of tubulysin were synthesized. Evans' oxazolidinone chemistry was employed for the stereoselective synthesis of Cbz-beta-homovaline in Tuv fragment. A crystal structure of the Tup fragment was obtained.</p><p> Cyclin dependent kinase 5 (CDK5) is one of the kinases that can hyperphosphorylate tau. Selective inhibition of the CDK5/p25 complex may be a useful component for Alzheimer's disease therapy. Benzimidazole based analogs of the known non-selective CDK5 inhibitor (R)-Roscovitine were designed. Synthesis of 6-benzyl substituted benzimidazole analogs was developed and two compounds were synthesized in this series. Two methods of the synthesis of 6-(2-hydroxy-1-alkyl)amino substituted benzimidazole analogs were developed.","abstract_has_math":false,"creators":["Yi, Shuyan"],"institution":null,"degree_name":"MS","degree_level":"Immediate Access","degree_discipline":"Medicinal Chemistry","degree_department":null,"school":null,"contributors":["Patrick Flaherty","Aleem Gangjee","Marc Harrold","David Lapinsky"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009-01-01T08:00:00Z","date_published":"2009-01-01T08:00:00Z","updated_at":"2026-07-24T02:10:43Z","subjects":["Kinase","Benzimidazole","Cyclin dependent kinase","Alzheimer's disease","Tubulysin","Neurofibrillary tangles"],"languages":["English"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dsc.duq.edu/etd/1392","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Patrick Flaherty","Aleem Gangjee","Marc Harrold","David Lapinsky"]},{"key":"dc:creator","label":"Author","values":["Yi, Shuyan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2018-03-28T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Medicinal Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Immediate Access"]},{"key":"thesis:degree_name","label":"Degree Name","values":["MS"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Kinase","Benzimidazole","Cyclin dependent kinase","Alzheimer's disease","Tubulysin","Neurofibrillary tangles"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dsc.duq.edu/etd/1392"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["This thesis describes the design and synthesis of 1,4,6-trisubstituted benzimidazoles as CDK5 inhibitors and the progress toward the total synthesis of tubulysin D.
Tubulysin is a natural product with potential anti-cancer activity. The two gamma-amino acids in the Tuv and Tup fragments of tubulysin were synthesized. Evans' oxazolidinone chemistry was employed for the stereoselective synthesis of Cbz-beta-homovaline in Tuv fragment. A crystal structure of the Tup fragment was obtained.
Cyclin dependent kinase 5 (CDK5) is one of the kinases that can hyperphosphorylate tau. Selective inhibition of the CDK5/p25 complex may be a useful component for Alzheimer's disease therapy. Benzimidazole based analogs of the known non-selective CDK5 inhibitor (R)-Roscovitine were designed. Synthesis of 6-benzyl substituted benzimidazole analogs was developed and two compounds were synthesized in this series. Two methods of the synthesis of 6-(2-hydroxy-1-alkyl)amino substituted benzimidazole analogs were developed."]},{"key":"dc:title","label":"Title","values":["Design and Synthesis of Benzimidazoles as CDK5 Inhibitors and Progress toward the Total Synthesis of Tubulysin D"]}]}],"canonical_facts":{"dc:contributor":["Patrick Flaherty","Aleem Gangjee","Marc Harrold","David Lapinsky"],"dc:creator":["Yi, Shuyan"],"dc:date.available":["2018-03-28T07:00:00Z"],"dc:description.abstract":["This thesis describes the design and synthesis of 1,4,6-trisubstituted benzimidazoles as CDK5 inhibitors and the progress toward the total synthesis of tubulysin D.
Tubulysin is a natural product with potential anti-cancer activity. The two gamma-amino acids in the Tuv and Tup fragments of tubulysin were synthesized. Evans' oxazolidinone chemistry was employed for the stereoselective synthesis of Cbz-beta-homovaline in Tuv fragment. A crystal structure of the Tup fragment was obtained.
Cyclin dependent kinase 5 (CDK5) is one of the kinases that can hyperphosphorylate tau. Selective inhibition of the CDK5/p25 complex may be a useful component for Alzheimer's disease therapy. Benzimidazole based analogs of the known non-selective CDK5 inhibitor (R)-Roscovitine were designed. Synthesis of 6-benzyl substituted benzimidazole analogs was developed and two compounds were synthesized in this series. Two methods of the synthesis of 6-(2-hydroxy-1-alkyl)amino substituted benzimidazole analogs were developed."],"dc:identifier":["https://dsc.duq.edu/etd/1392"],"dc:language":["English"],"dc:subject":["Kinase","Benzimidazole","Cyclin dependent kinase","Alzheimer's disease","Tubulysin","Neurofibrillary tangles"],"dc:title":["Design and Synthesis of Benzimidazoles as CDK5 Inhibitors and Progress toward the Total Synthesis of Tubulysin D"],"thesis:degree_discipline":["Medicinal Chemistry"],"thesis:degree_level":["Immediate Access"],"thesis:degree_name":["MS"]},"updated_at":"2026-07-24T02:10:43Z"}