Structure and synthesis of Gunnera perpensa secondary metabolites.
The project focused on the isolation, characterization and synthesis of secondary metabolites of Gunnera perpensa L. (Gunneraceae), a South African medicinal plant used by many South African women to induce or augment labour and as an antenatal medication to tone the uterus. From the methanol extracts of the rhizomes we have isolated the compounds Z-venusol, methyl lespedezate, 4-6>-/?-D-glucopyranosyl-3,3',4'-tri-0- methylellagic acid and punicallagin. Structural elucidation of the compounds was performed using NMR spectroscopy. The presence of ellagic acid derivatives and hydrolysable tannins have not previously been reported from the family Gunneraceae. The study also focuses on the development of an HPLC analytical method to fingerprint the crude extracts of G perpensa. This method was used to determine the chemical composition of the rhizomes of the G. perpensa collected in different parts of South Africa. It is clear from the HPLC study that the rhizomes contain large concentrations of the hydrolysable tannin punicalagin and the second most abundant metabolite was Z-venusol. However, it was observed from plants collected in different regions that the ratio between punicalagin and Z-venusol differs substantially in the different extracts. An ellagic acid derivative isolated from G. perpensa contains a biaryl structure derived from gallic acid. The synthesis described in this thesis focused on reaction methods to access unsymmetrical biaryls and two synthetic routes were investigated - one that relies on the Ullmann reaction and the second that uses the Heck coupling reaction. Success of this coupling reaction towards the formation of ellagic acid derivatives was accomplished by the Heck coupling reaction method. One of the most important considerations towards the synthesis was the manipulation of hydroxyl groups of gallic acid by selective protection reactions that provide entry to the aforementioned preparation of unsymmetrical ellagic acid derivatives.