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(Unpublished)
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.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| George Rosenker, Kara M. | georgkm@me.com | | |
|
| ETD Committee: |
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| Date: |
30 January 2014 |
| Date Type: |
Publication |
| Defense Date: |
7 November 2013 |
| Approval Date: |
30 January 2014 |
| Submission Date: |
11 November 2013 |
| Access Restriction: |
5 year -- Restrict access to University of Pittsburgh for a period of 5 years. |
| Number of Pages: |
237 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
PhD - Doctor of Philosophy |
| Thesis Type: |
Doctoral Dissertation |
| Refereed: |
Yes |
| Uncontrolled 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 |
| Date Deposited: |
30 Jan 2014 21:45 |
| Last Modified: |
30 Jan 2019 06:15 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/19989 |
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