eprintid: 6256 rev_number: 4 userid: 6 dir: disk0/00/00/62/56 datestamp: 2011-11-10 19:30:54 lastmod: 2016-11-15 13:35:55 status_changed: 2011-11-10 19:30:54 type: thesis_degree metadata_visibility: show contact_email: thgraham@pitt.edu item_issues_count: 0 eprint_status: archive creators_name: Graham, Thomas H. creators_email: thgraham@pitt.edu creators_id: THGRAHAM title: The Synthesis of Oxazole-containing Natural Products ispublished: unpub divisions: sch_as_chemistry full_text_status: public keywords: disorazol; macrodiolide; tubulin; anti-cancer; Sorangium cellulosum abstract: The first section describes the synthesis of the C1' to C11' side chain of leucascandrolide A. The key step of the synthesis is a modified Robinson-Gabriel synthesis of the oxazole. The C1' to C11' side chain was constructed in 9 steps and 7% overall yield.The second section describes the synthesis of 2-alkynyl oxazoles and subsequent transformations into a variety of useful motifs. The conjugate addition of nucleophiles to 2-alkynyl oxazoles under basic conditions affords vinyl ethers, vinyl thioethers and enamines. The addition of ethanedithiol affords dithiolanes that can be transformed into ethyl thioesters and ketones. Nucleophilic additions of thiols to 2-alkynyl oxazolines affords oxazoline thioethers. Additions of halides under acidic conditions stereoselectively affords vinyl halides that can be further transformed by Sonogashira cross-coupling reactions.The third section describes the synthesis of (-)-disorazole C1 and analogs. The macrocycle was constructed with minimal protecting group manipulations, using mild esterification and Sonogashira cross-coupling reactions. The convergent synthesis of disorazole C1 allowed for the synthesis of additional analogs. These analogs include the C14-t-butyl and C17-18-cyclopropane derivatives. Results from preliminary biological evaluations of synthetic intermediates, analogs and derivatives are also discussed. date: 2006-06-01 date_type: completed institution: University of Pittsburgh refereed: TRUE etdcommittee_type: committee_chair etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_type: committee_member etdcommittee_name: Wipf, Peter etdcommittee_name: Lazo, John S. etdcommittee_name: Koide, Kazunori etdcommittee_name: Floreancig, Paul E. etdcommittee_email: pwipf@pitt.edu etdcommittee_email: lazo@pitt.edu etdcommittee_email: koide@pitt.edu etdcommittee_email: florean@pitt.edu etdcommittee_id: PWIPF etdcommittee_id: LAZO etdcommittee_id: KOIDE etdcommittee_id: FLOREAN etd_defense_date: 2006-01-05 etd_approval_date: 2006-06-01 etd_submission_date: 2006-01-04 etd_access_restriction: immediate etd_patent_pending: FALSE assigned_doi: doi:10.5195/pitt.etd.2011.6256 thesis_type: dissertation degree: PhD committee: Peter Wipf (pwipf@pitt.edu) - Committee Chair committee: John S. Lazo (lazo@pitt.edu) - Committee Member committee: Kazunori Koide (koide@pitt.edu) - Committee Member committee: Paul E. Floreancig (florean@pitt.edu) - Committee Member etdurn: etd-01042006-164032 other_id: http://etd.library.pitt.edu/ETD/available/etd-01042006-164032/ other_id: etd-01042006-164032 citation: Graham, Thomas H. (2006) The Synthesis of Oxazole-containing Natural Products. Doctoral Dissertation, University of Pittsburgh. (Unpublished) document_url: http://d-scholarship-dev.library.pitt.edu/6256/1/grahamth_etd2006.pdf