Studies on the viability of cyclopropane-containing peptidomimetics and application of the vinylogous Mannich reaction to the syntheses of indolizidine natural products

dc.contributor.advisorMartin, Stephen F.en
dc.creatorReichelt, Andreasen
dc.date.accessioned2008-08-28T21:38:01Zen
dc.date.available2008-08-28T21:38:01Zen
dc.date.issued2003en
dc.descriptiontexten
dc.description.abstract1,2,3-Trisubstituted cyclopropanes have been previously incorporated into inhibitors of matrix metalloproteases, in order to mimic extended conformations of the peptide backbones and orient the amino acid side chains. Two reduced dipeptides, which are flexible analogues of these cyclopropane-containing peptidomimetics, were synthesized. Biological evaluation of the flexible compounds, the conformationally restricted peptidomimetics, and the parent inhibitor provided a deeper insight into the scope and limitation of cyclopropanecontaining replacements as mimics for peptide secondary structures. A concise enantiospecific synthesis of the angiotensin-converting enzyme inhibitor A58365A has been achieved. In the key step, a sequence involving a vinylogous Mannich reaction followed by a base-induced lactone–lactam rearrangement was applied to establish the indolizidine core of the molecule. A conceptually novel approach to the potent immunosuppressant FR901483 has been proposed. It has been demonstrated that an addition– vinylogous Mannich reaction sequence can be employed to obtain unsymmetrical α,α-disubstituted amines from carbamate-protected lactams. This sequence could be applied to the diastereoselective generation of one of the bridgehead centers in FR901483.
dc.description.departmentChemistry and Biochemistryen
dc.description.departmentChemistryen
dc.format.mediumelectronicen
dc.identifierb57198494en
dc.identifier.oclc56908038en
dc.identifier.proqst3118065en
dc.identifier.urihttp://hdl.handle.net/2152/882en
dc.language.isoengen
dc.rightsCopyright is held by the author. Presentation of this material on the Libraries' web site by University Libraries, The University of Texas at Austin was made possible under a limited license grant from the author who has retained all copyrights in the works.en
dc.subject.lcshCyclopropaneen
dc.subject.lcshPeptides--Synthesisen
dc.subject.lcshMannich reactionen
dc.titleStudies on the viability of cyclopropane-containing peptidomimetics and application of the vinylogous Mannich reaction to the syntheses of indolizidine natural productsen
dc.type.genreThesisen

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