Ph.D. (Chemistry) / The aim of this study was the development of stereoselective routes for the asymmetric synthesis of chiral precursors of I1-deoxy-1l-thiaprostaglandins and albomysin di, using carbohydrates as chiral building blocks. A brief overview of known stereocontrolled routes for the synthesis of sulphur-containing monosaccharides and heterocyclic prostaglandin analogues is presented. Approaches to the stereocontrolled synthesis of I1-deoxy-11-thiaprostaglandins from Larabinose are described. Special topics in this part of the study include approaches to the preparation of chiral tetrahydrothiophenes. The 1,4-diol 5-0-benzoyl-3-deoxy-3-C-(carboxymethyl- 2,3-y-lactone)-L-lyxitol (146a), was identified as a possible chiral building block for the proposed route towards 11-thiaprostaglandins. New groups for the activation of the hydroxyl functions of the 1,4-diol in order to introduce the ring sulphur atom via a 1thiobenzyl ether, were investigated. The l,4-diol was subsequently transformed into a 1,4dimesylate and this compound proved to be the most suitable for the generation of the tetrahydrothiophene unit. This investigation resulted in an efficient synthesis of 11thiaprostaglandin precursors using glucose as a chiral building block. In the second part of the investigation, approaches to the stereoselective synthesis of a potential precursor for the synthesis of albomysin dr are described. An investigation of the selective acylation of acyclic pentoses are also presented. The aim of this study was the regioselective introduction of a leaving group, for example a tosylate, in acyclic derivatives of pentose without protecting any of the secondary hydroxyl groups. This strategy would make intramolecular cyclisations possible with a suitable nycleophile present on C-l. Some of the compounds in the pentose series investigated, furnished dibutyltin complexes which were regioselectively acylated in an efficient manner. Starting from L-arabinose an alternative strategy for the synthesis of a precursor for the synthesis of aIbomysin di is also given. The synthesis involved the preparation of 1-0-acetyl2,3, 5-tri-O-benzoyl-4-thio-xylofuranose, followed by conversion to the required nucleoside.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uj/uj:4310 |
| Date | 12 March 2014 |
| Creators | Swanepoel, Anna Dorathea |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
| Rights | University of Johannesburg |
Page generated in 0.0022 seconds