<p> Arginase is a manganese-containing enzyme that catalyzes the hydrolysis of L-arginine to yield L-ornithine and urea. It has been suggested that inhibition of arginase could be of therapeutic utility, and an arginase inhibitor is currently in phase I clinical trials for a variety of cancer subtypes. To date, the most promising inhibitors reported in the literature are α,α-disubstituted arginine analogs with a boronic acid warhead in place of the substrate guanidine group. However, the stereoselective approaches reported to date for this class of compounds have significant limitations and novel methods are needed. This research investigates two approaches: a route towards α,α-disubstituted amino acids via the enzyme-catalyzed desymmetrization of a meso diester and the utilization of the Petasis borono-Mannich reaction as an alternate enantioselective route for mono-substituted analogs.</p><p>
| Identifer | oai:union.ndltd.org:PROQUEST/oai:pqdtoai.proquest.com:10283110 |
| Date | 19 October 2017 |
| Creators | Guerrera, Cessandra |
| Publisher | Southern Connecticut State University |
| Source Sets | ProQuest.com |
| Language | English |
| Detected Language | English |
| Type | thesis |
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