Synthesis of Novel Analogs of Belactosin A and Carfilzomib

dc.contributor.advisor Dunlap, Norma Yadab, Mahesh Kumar
dc.contributor.committeemember Handy, Scott
dc.contributor.committeemember Bicker, Kevin
dc.contributor.department Chemistry en_US 2018-06-05T20:04:55Z 2018-06-05T20:04:55Z 2018-02-17
dc.description.abstract Belactosin 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.abstract Several 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. M.S.
dc.publisher Middle Tennessee State University
dc.subject MAHESH
dc.subject.umi Chemistry
dc.subject.umi Organic chemistry
dc.thesis.degreegrantor Middle Tennessee State University
dc.thesis.degreelevel Masters
dc.title Synthesis of Novel Analogs of Belactosin A and Carfilzomib
dc.type Thesis
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