Item – Theses Canada

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OCLC number
1007094266
Link(s) to full text
LAC copy
LAC copy
Author
Coltart, Donald M.,1969-
Title
Synthetic studies on angiotensin-converting enzyme inhibitors, pyridines, and peptides.
Degree
Ph. D. -- University of Alberta, 2000
Publisher
Ottawa : National Library of Canada = Bibliothèque nationale du Canada, [2002]
Description
4 microfiches
Notes
Includes bibliographical references.
Abstract
The first chapter of this thesis describes the total synthesis of the angiotensin-converting enzyme inhibitors A58365A (1) and A58365B (2), in both racemic and optically pure form. The synthesis of each compound was achieved from the advanced intermediate 3. This species was elaborated to both the five and six-membered enamides 4, which subsequently underwent radical cyclization to afford vinyl stannanes 6. Protodestannylation of 6 gave the exocyclic olefins 7, which were then elaborated to the target compounds 1 and 2. The optical purity of the nonracemic final products was established by analytical HPLC using a chiral, nonracemic stationary phase.* The final chapter of this thesis describes our preliminary investigations into peptide segment coupling by prior ligation and proximity-induced intramolecular acyl transfer. Several compounds of the general type 10 were prepared, each having a different thiol tether attached to the terminal amino group. These underwent ligation by thioester exchange with a thioester ( 11) to give an intermediate (12) in which the appropriate amino and acyl groups were in proximity. Intramolecular acyl transfer could then occur, thereby coupling the two components, by formation of a new peptide bond, to give 13.* The appendix of this thesis describes the synthesis of 2-methoxy-4-methylpyridine-3-carbonitrile (8) and its conversion, by way of alkylation of the C-4 methyl group, into the pyridyl acetic ester 9.* *Please refer to dissertation for diagrams.
ISBN
0612595722
9780612595729