This thesis describes the development of four synthetic routes towards the syntheses of N, N' ethylene-bridged dipeptides and their application towards the synthesis of such 2-oxopiperazine derivatives on solid support. / The first route proceeds by the generation of an N-allyl substituted amino ester, its coupling to a second amino acid and subsequent oxidative cleavage of the carbon-carbon double bond to provide the cyclized product. The second route proceeds by the generation of 4-nitrobenzenesulfonamide dipeptides and their alkylation by 1,2-dibromoethane. The third route proceeds by a Mitsunobu reaction between sulfonamide dipeptides and bromoethanol followed by treatment with DBU to generate the desired 2-oxopiperazine derivative. The fourth route again uses the sulfonamide dipeptide esters as intermediates. This time an allyl group is installed and this is then converted to the diol that is subsequently oxidatively cleaved by action of sodium periodate. Alternatively, the allyl group is converted to the epoxide that is treated with periodic acid to effectively carry out the same transformation. / The synthesis of these ethylene-bridged dipeptides was also carried out on solid support in an effort to create a combinatorial library of such constrained peptidomimetics. The partial success of the above-mentioned approaches on solid support is described. / Finally, the synthesis of two new analogs of Thyrotropin Releasing Hormone (TRH) incorporating the 2-oxopiperazine ring is described.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.35983 |
| Date | January 1999 |
| Creators | Bhatt, Ulhas. |
| Contributors | Just, George (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Chemistry.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001737939, proquestno: NQ55303, Theses scanned by UMI/ProQuest. |
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