Synthesis of Novel Analogs of Belactosin A and Carfilzomib
Synthesis of Novel Analogs of Belactosin A and Carfilzomib
dc.contributor.advisor | Dunlap, Norma | |
dc.contributor.author | Yadab, Mahesh Kumar | |
dc.contributor.committeemember | Handy, Scott | |
dc.contributor.committeemember | Bicker, Kevin | |
dc.contributor.department | Chemistry | en_US |
dc.date.accessioned | 2018-06-05T20:04:55Z | |
dc.date.available | 2018-06-05T20:04:55Z | |
dc.date.issued | 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. | |
dc.description.degree | M.S. | |
dc.identifier.uri | http://jewlscholar.mtsu.edu/xmlui/handle/mtsu/5674 | |
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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