D.Phil. / The objective of the research described in the first part of this thesis was to develop a general method utilising palladium catalysed reactions for the synthesis of the anti-cancer compound, lavendamycin and analogs thereof. Therefore, the development of a general route to synthetic euivalents of the lavendamycin AB quinoline system, 2-hydroxyquinolines, with potential for coupling to the CDE or CD moiety, was addressed. The first protocol for the synthesis of 2-hydroxyquinolines invloved to the use of appropriately substituted o-nitrophenyltriflates (readily prepared from phenols) in a Heck reaction under neutral conditions followed by a one-pot reduction and cyclisation step. The synthetic potential of such an approach was demonstrated by the preparation of a suitable lavendamycin AB synthon from commecially avalaible guiacol. A second general strategy towards the synthesis of the AB synthon utilising a performed ring system commecially available 8-hydroxyquinoline has been successfully developed. This approach requiring the introduction of a suitable leaving group in the 2-position involved the following sequence of reactions: protection of 8-hydroxyl group N-oxidation, and a rearrangement step. This methodology yielded five different key intermediates all possessing suitable functionality in the 2 position which would allow further cross-coupling to an appropriate CDE ring equivalent.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uj/uj:3449 |
| Date | 04 September 2012 |
| Creators | Marais, Wilhelmina |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
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