eprintid: 19989 rev_number: 11 userid: 2620 dir: disk0/00/01/99/89 datestamp: 2014-01-30 21:45:40 lastmod: 2019-01-30 06:15:03 status_changed: 2014-01-30 21:45:40 type: thesis_degree metadata_visibility: show contact_email: georgkm@me.com item_issues_count: 0 eprint_status: archive creators_name: George Rosenker, Kara M. creators_email: georgkm@me.com title: Regioselective Functionalizations of Heterocycles and Applications in Methodology, Medicinal Chemistry, and Natural Product Synthesis ispublished: unpub divisions: sch_as_chemistry full_text_status: public keywords: palladium catalysis, palladium cross-coupling, heterocycles, regioselectivity, quinazoline, Cdc25B inhibitor, isoquinoline, protein kinase D, small molecule inhibitor, pyrimidine, pyridine, CID755673, thiazepinothiophenopyrimidinone, chemical diversity, hydrozirconation, isoindolinones, metathesis, N-acyliminium ion, stemona alkaloid, sessilifoliamide C, lactam abstract: The first two sections of this dissertation describe the development of a regioselective palladium-catalyzed cross-coupling strategy to access highly functionalized heterocycles. This method was successfully applied to 2,4,7-trichloroquinazoline, allowing for the efficient synthesis of quinazolines bearing functionality in specific positions of the heterocyclic ring. The strategy was also extended to 1,3,6-trichloroquinoline for the synthesis and scale-up of a promising 3-aminoisoquinolin-1(2H)-one inhibitor of the dual-specificity phosphatase Cdc25B. The third section of this dissertation describes the design and synthesis of novel thieno[3,2-d]pyrimidine- and thieno[3,2-c]pyridine-based analogs for the inhibition of protein kinase D. A small library of analogs was prepared to assess the structure-activity relationship, and one analog was tested in vivo. The fourth section of this dissertation discusses the investigation of an unusual alkene isomerization process, which occurred during the ring-closing metathesis for the preparation of a tricylic isoindolinone scaffold. The final section of this thesis details our work towards the synthesis of Stemona alkaloids. In particular, a second-generation approach to sessilifoliamide was achieved. date: 2014-01-30 date_type: published pages: 237 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: Curran, Dennis P. etdcommittee_name: Floreancig, Paul E. etdcommittee_name: Wang, Q. Jane etdcommittee_email: pwipf@pitt.edu etdcommittee_email: curran@pitt.edu etdcommittee_email: florean@pitt.edu etdcommittee_email: qjw1@pitt.edu etdcommittee_id: PWIPF etdcommittee_id: CURRAN etdcommittee_id: FLOREAN etdcommittee_id: QJW1 etd_defense_date: 2013-11-07 etd_approval_date: 2014-01-30 etd_submission_date: 2013-11-11 etd_release_date: 2014-01-30 etd_access_restriction: 5_year etd_patent_pending: FALSE thesis_type: dissertation degree: PhD citation: George Rosenker, Kara M. (2014) Regioselective Functionalizations of Heterocycles and Applications in Methodology, Medicinal Chemistry, and Natural Product Synthesis. Doctoral Dissertation, University of Pittsburgh. (Unpublished) document_url: http://d-scholarship-dev.library.pitt.edu/19989/1/rosenkerkmg_etd2013.pdf