The aim of the project was to synthesize warburganal, a natural product isolated from the Warburgia plants native to Venda, known as a potent molluscicide, in a new, cheaper and more efficient way to be used in the ongoing war against bilharzia. A synthetic pathway beginning with geraniol as the starting material was planned to afford a 7-step route. The first step involved the substitution of a bromine group for a hydroxyl group. Geranyl bromide underwent an alkylation step with the dianion of methyl acetoacetate to afford methyl 3-oxo-7, II-dimethyldodeca-6E, IO-dienoate. The . next Lewis acid-catalyzed step involved formation of the bicyclic decalin ring system, methyl (IR* ,4aS*,8aS*)-2-oxo-5,5,8a-trimethyldecahydronaphthalene-I-carboxylate. The next step was to add a hydroxyl group alpha to the ester, the a-OH being vitally important to the biological activity of warburganal. This step proved to be unsuccessful
with the methodology used. A change in tactics was obviously required and initially protection of the ketone as an acetal was attempted. Instead of the expected acetal product, an epimer of the decalin structure above, namely, methyl (IS*,4aS*,8aS*)-2-oxo-5,5,8a-trimethyldecahydronaphthalene-I-carboxylate was isolated. This epimer seems to form under acidic as well as basic conditions and was also isolated from an a-hydroxylation reaction that employed KH and MoOPH.
Most of the steps were attempted on model compounds to enable the conditions to be optimized prior to attempting the reaction on the warburganal precursor. It was soon discovered that for reasons as yet unknown, the reactions that worked on the model compounds did not always work on the warburganal precursors, although the model
compounds possessed functional groups that best simulated those possessed by warburganal. The progress reported towards the synthesis of warburganal highlights the many difficulties encountered when introducing the requisite functional groups on to the decalin ring skeleton to afford warburganal i. e. the a-hydroxyl and p-aldehyde moieties
and the a,p-unsaturated aldehyde. Although the planned synthetic pathway was not entirely successful, the pitfalls encountered are discussed and potential solutions are presented. A number of interesting and unexpected compounds were isolated en route and ideas are discussed that may well culminate in an efficient synthesis of warburganal. / Thesis (Chemistry)-University of Natal, Pietermaritzburg, 1998.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:ukzn/oai:http://researchspace.ukzn.ac.za:10413/5936 |
| Date | January 1998 |
| Creators | Paulton, Anne-Mary. |
| Contributors | Emslie, N. D., Gravestock, David. |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | English |
| Type | Thesis |
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