This thesis has two parts. The first deals with the conformational behaviour of Nsubstituted and N-unsubstituted bis-tetrahydroisoquinoline derivatives under neutral and acidic conditions and the second describes the design, synthesis and structural characterization of a new class of N-ureidyl bis-tetrahydroisoquinoline derivatives, potential catch and release agents. Four N-alkyl derivatives, two of which were new, were studied in detail for their conformational behaviour and their spectroscopic properties compared extensively with N-unsubstituted compounds. NMR chemical shift changes and vicinal spin couplings were measured and related to conformational change within the heterocyclic rings and about the central C1-C1' axis. The basicity of the amines were determined through pKa measurements, and differences between the behaviour of secondary and tertiary amine examples discussed. Analysis of titration results revealed the formation of discrete 1:1 and 1:2 complexes between the secondary examples and added carboxylic acids, but only 1:1 complexes in the case of tertiary amine complexes. Monitoring of changes in conformation with incremental addition of acid provided new understanding about modes of binding. A new class of nine ureidyl bis-tetrahydroisoquinoline derivatives has been prepared. These contain N'-aryl and N'-adamantyl urea groups attached to the bisisoquinoline core through alkyl linker groups with varying length. The conformation of these derivatives were heavily dependent upon the linker length while the nature of the urea group (in one case a thiourea) played a small role in the preferred conformation of the bis-tetrahydroisoquinoline. Three non-isoquinoline derived model ureidyl amine systems were also synthesized for comparative studies. Four partner ureidyl acids were prepared and their pKa values in DMSO were measured. Studies of the interaction of the ureidyl acids with the ureidyl amines revealed that the chain length of the ureidyl bistetrahydroisoquinoline linker played a small role while the remote aryl and adamantyl groups of both acids and amines played a more important role. DMSO was found to interfere with the normal conformations of the ureidyl bis-tetrahydroisoquinolines and with the interaction of the ureidyl bis-tetrahydroisoquinolines with their partner ureidyl acids in deuterochloroform. The latter studies will provide the basis for future design of catch-and-release agents derived from bis-tetrahydroisoquinolines.
| Identifer | oai:union.ndltd.org:ADTP/257334 |
| Date | January 2007 |
| Creators | Chan, Benjamin Kin Heng, Chemistry, Faculty of Science, UNSW |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | http://unsworks.unsw.edu.au/copyright, http://unsworks.unsw.edu.au/copyright |
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