Maskrey, Taber
(2021)
Synthetic Studies of Heterocyclic and Bioactive Agents.
Doctoral Dissertation, University of Pittsburgh.
(Unpublished)
Abstract
This dissertation describes a novel one-pot preparation of bicyclic heterocycles and improved synthetic procedures for the production of compounds possessing established biological activity. A five-component condensation reaction was discovered that follows a mechanistic sequence starting with a Biginelli reaction and ending in a Diels-Alder reaction to form a new class of bicyclic heterocycles. New protocols were developed to synthesize the bioactive compounds Gefitinib and analogs of JP4-039. The FDA approved EGFR inhibitor Gefitinib was synthesized on a pilot-plant scale using a more efficient synthetic sequence and fewer hazardous reagents. A shorter synthetic sequence to ferroptosis inhibitors, JP4-039 and related analogs, was developed with a key vinylogous Mannich reaction utilizing an oxazolidinone auxiliary. The biological activity of new ferroptosis inhibitors was used to generate a structure-activity relationship (SAR) hypothesis.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
3 May 2021 |
| Date Type: |
Publication |
| Defense Date: |
17 March 2021 |
| Approval Date: |
3 May 2021 |
| Submission Date: |
15 March 2021 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| 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: |
5-component-condensation reaction, Gefitinib, JP4-039, ferroptosis, vinylogous Mannich reaction |
| Date Deposited: |
03 May 2021 14:46 |
| Last Modified: |
03 May 2021 14:46 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/40373 |
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