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Synthesis and Biological Evaluation of a Furanosteroid Library of PI3-kinase Inhibitors and Studies Toward the Total Synthesis of 9-Normethylpleurotin

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 (Unpublished)

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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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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Vargas, Julia Ljlv19@pitt.eduJLV19
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairWipf, Peter
Committee MemberWilcox, Craig
Committee MemberFloreancig, 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:, etd-04142009-194046
Date Deposited: 10 Nov 2011 19:37
Last Modified: 15 Nov 2016 13:40


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