Synthesis of Novel Analogs of Belactosin A and Carfilzomib

dc.contributor.advisorDunlap, Norma
dc.contributor.authorYadab, Mahesh Kumar
dc.contributor.committeememberHandy, Scott
dc.contributor.committeememberBicker, Kevin
dc.contributor.departmentChemistryen_US
dc.date.accessioned2018-06-05T20:04:55Z
dc.date.available2018-06-05T20:04:55Z
dc.date.issued2018-02-17
dc.description.abstractBelactosin A, a naturally occurring proteasome inhibitor with potent anti-tumor activity, was discovered in the late 1980’s. The key structural features of the natural product include a cyclopropane ring with a terminal β-lactone “serine trap”. Activity is conferred by acylation of the β-lactone with a threonine of the proteasome. Carfilzomib is a tetrapeptide epoxyketone, and an analog of epoxomicin with improved properties. In phase I and phase II clinical trials, carfilzomib exhibited higher selectivity, equal potency and less peripheral neuropathy than bortezomib and salinosporamide. Its activity is due to the formation of a highly stable six membered morpholine ring by the interaction between epoxyketone, free hydroxy and α-amino groups of the threonine.
dc.description.abstractSeveral syntheses of belactosin A and carfilzomib have been reported, however only a handful of analogs have been reported. An approach to the synthesis of novel hybrid analogs is reported here, with the synthesis of phenylalanine, leucine and valine cyclopropyl analogs of belactosin A with the epoxyketone of carfilzomib. Key steps in the synthetic route include a cyclopropanation and formation of an enone followed by epoxidation.
dc.description.degreeM.S.
dc.identifier.urihttp://jewlscholar.mtsu.edu/xmlui/handle/mtsu/5674
dc.publisherMiddle Tennessee State University
dc.subjectMAHESH
dc.subject.umiChemistry
dc.subject.umiOrganic chemistry
dc.thesis.degreegrantorMiddle Tennessee State University
dc.thesis.degreelevelMasters
dc.titleSynthesis of Novel Analogs of Belactosin A and Carfilzomib
dc.typeThesis

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