Vargas, Julia L
(2009)
Synthesis and Biological Evaluation of a Furanosteroid Library of PI3-kinase Inhibitors and Studies Toward the Total Synthesis of 9-Normethylpleurotin.
Master's Thesis, University of Pittsburgh.
(Unpublished)
Abstract
A library of furanosteroids was synthesized by oxidation of a catechol and a 4-hydroxycoumarin with potassium ferricyanide. Further diversification of these substrates was achieved through various acetalization reactions. The resultant compounds were then evaluated as potential inhibitors against PI3-kinase using a competitive ELISA assay. As an extension to this initial library, a subset of cromolyn derivatives were synthesized and subsequent biological evaluation of these compounds is underway. Secondly, studies have been ongoing to achieve the total synthesis of pleurotin featuring an in situ hydrozirconation-transmetallation-aldehyde addition process followed by an Ireland-Claisen rearrangement and finally an intramolecular Diels-Alder cyclization. Previous difficulty with the installation of the C8-C9-C21 side-chain and the configuration at the C10 center led us to pursue the 9-normethylpleurotin analog. In our efforts to address this stereochemistry issue difficulties arose in scaling up the initial route to our key starting aldehyde for the hydrozirconation-transmetallation-aldehyde addition. Therefore an alternative route was developed utilizing a benzyne-furan [4 + 2]-cycloaddition.
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Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
| Title | Member | Email Address | Pitt Username | ORCID |
|---|
| Committee Chair | Wipf, Peter | | | | | Committee Member | Wilcox, Craig | | | | | Committee Member | Floreancig, Paul | | | |
|
| Date: |
5 June 2009 |
| Date Type: |
Completion |
| Defense Date: |
30 March 2009 |
| Approval Date: |
5 June 2009 |
| Submission Date: |
14 April 2009 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
| Degree: |
MS - Master of Science |
| Thesis Type: |
Master's Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
benzyne cycloaddition; Furanosteroid; PI3-kinase inhibitor; Pleurotin; Thioredoxin Reductase; Wortmannin |
| Other ID: |
http://etd.library.pitt.edu/ETD/available/etd-04142009-194046/, etd-04142009-194046 |
| Date Deposited: |
10 Nov 2011 19:37 |
| Last Modified: |
15 Nov 2016 13:40 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/7165 |
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