SYNTHETIC APPROACHES TO CYCLOPROPYL PEPTIDOMIMETICS AS 20S PROTEASOME INHIBITORS

dc.contributor.advisorDunlap, Norma K
dc.contributor.authorAnwar, Avraz F
dc.contributor.committeememberBicker, Kevin L
dc.contributor.committeememberHandy, Scott
dc.date.accessioned2021-04-15T04:01:41Z
dc.date.available2021-04-15T04:01:41Z
dc.date.issued2021
dc.date.updated2021-04-15T04:01:41Z
dc.description.abstractProteasome inhibitors are a relatively new class of chemotherapeutics with only three drugs currently on the market. Belactosin A, a natural product found in Streptomyces sp., possesses anti-tumor effects due to its proteasome inhibition properties, however it is not used clinically due to its toxicity. This led to several syntheses of belactosin A analogs in hopes of similar efficacy and lower toxicity. Most reported syntheses require a substantial number of steps to synthesize the cyclopropyl backbone and the b-lactone warhead of belactosin A. An efficient stereoselective cyclopropanation of amino acid enones that undergo a Michael-induced ring closure is reported here with the use of cinchona alkaloids as a catalysts, and lactonization of L-threonine to afford the a-substituted b-lactone warhead. The proposed synthetic route of the L-threonine-derived b-lactone analog of belactosin A is significantly more efficient compared to alternative analogs reported in literature.
dc.description.degreeM.S.
dc.identifier.urihttps://jewlscholar.mtsu.edu/handle/mtsu/6401
dc.language.rfc3066en
dc.publisherMiddle Tennessee State University
dc.source.urihttp://dissertations.umi.com/mtsu:11402
dc.subjectBelactosin A
dc.subjectPeptidomimetics
dc.subjectProteasome inhibitors
dc.subjectStereoselective cyclopropanations
dc.subjectOrganic chemistry
dc.thesis.degreelevelmasters
dc.titleSYNTHETIC APPROACHES TO CYCLOPROPYL PEPTIDOMIMETICS AS 20S PROTEASOME INHIBITORS

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