Studies in marine diterpene chemistry
- Authors: Van Wyk, Albert Wynand Wincke
- Date: 2008
- Subjects: Natural products Diterpenes Mollusks Marine metabolites Chemical oceanography
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4354 , http://hdl.handle.net/10962/d1005019
- Description: This thesis comprises both a natural product investigation and a synthetic component. The natural product investigations are presented in Chapters Two and Three. In Chapter Two the isolation and spectroscopic identification of the new isocopalane diterpene 12S,13R,14Sisocopalan- 13-ol-12,14-diacetate (2.1) and two known 3-(14S)-isocopal-12-ene-15-oyl-1- acetyl-sn-glycerol (2.2) and 3-(14S)-isocopal-12-ene-15-oyl-2-acetyl-sn-glycerol (2.3) from a single, large, unidentified sub-Antarctic nudibranch, collected near Marion Island, approximately 2000 km south of Cape Town are described. Chapter Three discusses the isolation, spectroscopic structure elucidation and anti-oesophageal cancer activity (3.1-3.4 only) of two known labdane diterpenes 6β,7α-diacetoxylabda-8,13E-dien-15-ol (3.1) and 2α,6β,7α-triacetoxylabda-8,13E-dien-15-ol (3.2) and one new 6β,7α,15-triacetoxylabda 8,13E-diene (3.3), as well as new 3α,11-dihydroxy-9,11-seco-cholest-4,7-dien-6,9-dione (3.4) and cholest 7-en-3,5,7-triol (3.5) from the endemic pulmonate mollusc, Trimusculus costatus. The absolute configuration of 3.2, and hence 3.1 and 3.3 (from biogenetic arguments) was determined through X-ray diffraction of a single crystal of the camphanate ester of 3.2. The absolute configuration of the secondary hydroxyl at C-3 of 3.4 was established using the Modified Mosher’s method. The synthetic component of the thesis commences in Chapter Four with the semi-synthesis of labdane diterpene nitriles 9α-cyano-15,16-epoxy-7β-hydroxylabda-13(16),14-dien-6-one (4.1), 9α-cyano-15,16-epoxy-7-hydroxylabda-7,13(16),14-trien-6-one (4.2) and 9α-cyano-15,16- epoxy-6β,7β dihydroxylabda-13(16),14-diene (4.3) from the terrestrial labdane diterpene, hispanolone (4.4). This work is an extension of previous synthetic studies directed towards the synthesis of T. costatus metabolites. Diterpenes 4.1-4.3 exhibited in planta activity against the economically important crop pathogens, Magnaporthea grisea and Puccinia recondita. Chapter Five describes the successful semi-synthesis of two isomeric marine molluscan labdane diterpene aldehyde metabolites, labd-13E-ene-8β-ol-15-al (5.1) and labd-13Z-ene- 8β-ol-15-al (5.2) from the commercially available, terrestrial plant derived, labdane diterpene manool (5.3). Diterpenes 5.1 and 5.2, originally isolated from the Mediterranean nudibranch,Pleurobranchaea meckelii and selected diterpenes arising from this synthesis were evaluated for their activity against an oesophageal cancer cell line (WHCO1). Chapter Six further develops the research discussed in Chapter Five, where ethyl 17-norabiet-13(15)-E-en-8β-ol- 16-oate (5.49) and ethyl 17-norabiet-13(15)-Z-en-8β-ol-16-oate (5.50) were first semisynthesized serendipitously. Based on their structural relationship to naturally occurring tricyclic diterpenes with anti-plasmodial activity, tricyclic diterpenes, 17-norpimaran-13α- ethoxy-8,16-olactone (6.6), 17-norisopimar-15-ene-8β,13β-diol (6.7), 17-norisopimarane- 8β,16-diol (6.8) and 17-norabiet-13(15)-ene-8β,16-diol (6.9) were semi-synthesized from the terrestrial labdane diterpene, 5.3, and critically evaluated for their antimalarial potential from parasite inhibition and haemolytic studies.
- Full Text:
The effect of geography, cultivation and harvest technique on the umckalin concentration and growth of pelargonium sidoides (Geraniaceae)
- Authors: White, Andrew Graeme
- Date: 2007
- Subjects: Pelargoniums , Geraniaceae , Botany -- South Africa -- Eastern Cape , Traditional medicine -- South Africa -- Eastern Cape , Medicinal plants -- South Africa -- Eastern Cape , Coumarins
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4234 , http://hdl.handle.net/10962/d1003803 , Pelargoniums , Geraniaceae , Botany -- South Africa -- Eastern Cape , Traditional medicine -- South Africa -- Eastern Cape , Medicinal plants -- South Africa -- Eastern Cape , Coumarins
- Description: Pelargonium sidoides DC. (Geraniaceae) root extracts are used in the Eastern Cape Province of South Africa as a traditional medicine for the treatment of respiratory tract and gastro-intestinal infections. Ethanolic extracts are used globally as herbal treatments for bronchitis, asthma and as an immune system booster. Despite documented exploitation of wild populations by illegal harvesters, this species has not been awarded a protected status. The high level of harvest in the years preceding this study prompted this investigation of the prospects for sustainable root harvest through wild harvest and greenhouse cultivation. A novel method was developed for the purification of umckalin, a bioactive constituent in root extracts, such that the root umckalin concentrations of wild and cultivated plants could be quantified by HPLC. As part of the cultivation experiments, the concentration of umckalin in roots was measured for plants across part of the species’ distribution range in the Eastern Cape Province. This survey revealed that root umckalin concentrations were inversely related to the average annual rainfall of the collection site (r² = 0.94, p = 0.007) and directly related to soil pH (r² = 0.97, p = 0.002). Thus, the possibility of inducing high umckalin concentrations in greenhouse-cultivated plants was investigated by subjecting plants to rapid and prolonged water stress treatments. Two leaf applied hormone treatments (cytokinin and gibberellin) and a root competition treatment with a fast growing annual (Conyza albida) were also investigated based on the potential function of umckalin in P. sidoides plants. These five treatments did not significantly affect root umckalin concentrations compared to well-watered controls. The results of further experiments suggested that umckalin production may have been influenced by the geographical origin and genetics of plants rather than environmental variation. Following wild harvest experiments, the regrowth of replanted shoots from which a standard proportion of the root was harvested showed that water availability affected shoot survival but not root regrowth rate. Regrowth rates were low, questioning the viability of wild harvest. In contrast, greenhouse cultivated plants showed ca. six times greater growth rates, supporting the cultivation of roots to supply future market demand.
- Full Text:
Structural and synthetic investigations of South African marine natural products
- Authors: Beukes, Denzil Ronwynne
- Date: 2000
- Subjects: Natural products -- South Africa Marine invertebrates -- South Africa Marine metabolites -- South Africa
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4350 , http://hdl.handle.net/10962/d1005015
- Description: A chemical investigation of six different marine invertebrates, collected along the South African coastline, resulted in the isolation and structural elucidation of fifteen previously undescribed secondary metabolites along with seven known compounds. The structures of the new metabolites were determined by a combination of spectroscopic and chemical methods. The endemic false limpet Siphonaria capensis was shown to contain two unusual polypropionate metabolites capensinone (162) and capensifuranone (163) as well as 2,4,6,8-tetramethyl-2-undecenoic acid (164) and the known polypropionates (E)- and (Z)siphonarienfuranone (149 and 161). Capensinone is the first example of a marine polypropionate containing a cyc1opentenone moiety. An investigation of the endemic South African soft coral Pieterfaurea unilobata yielded six new, highly oxygenated, pregnadiene sterols (180-185) and the known metabolite (169). Compounds 180-185 are the first pregnadienes obtained from the marine environment containing a C-7 substituent. An alternative procedure for the quick assignment of the absolute configuration at C-3 in this series of compounds was proposed. A companson of the pyrroloiminoquinone alkaloids of three undescribed l'}trunculid sponges resulted in the isolation of 3-dih¥drodiscorhabdin C (243), 3-dihydrodiscorhabdin B (244), discorhabdin H (197) and the previously reported alkaloids discorhabdin A (189) and discorhabdin D (192). While all three sponges were found to be morphologically different they all contained discorhabdin A as the major metabolite and discorhabdin H as one of their minor metabolites. It was found that a feature common to most of the South African latrunculid sponges is the reduction of the C-3 carbonyl gr,o up in some of the minor metabolites. The indole alkaloids, dilemmaones A-C (261-263), containing an unusual cyc1opentanone-indole skeleton, were isolated in trace amounts by bioassay guided fractionation of an extract obtained from a mixed collection of sponges collected near Cape Town. In an attempt to acquire more of these novel compounds for further investigation of their biological activity, several synthetic strategies towards their total synthesis were explored. A key feature of these approaches was the exploitation of the regioselective Gassman's artha-alkylation procedure for the introduction of an aromatic methyl substituent.
- Full Text:
A taxonomic study of Senecio speciosus, Senecio macrocephalus and possible hybrid populations using morphological data, toxicty tests and chromatography
- Authors: Lewis, Gillian Elizabeth
- Date: 1995
- Subjects: Senecio , Senecio -- Analysis , Shrimps , Artemia
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4209 , http://hdl.handle.net/10962/d1003778
- Description: The variation between populations of Senecio speciosus Willd., Senecio macrocephalus DC. and intermediate plants was investigated in a comparative study of morphological characters, toxicity of plant extracts to brine shrimps (Artemia salina) and chromatography of plant extracts. Specimens were collected at 18 localities in the Eastern Cape Province. All these specimens were examined morphologically and chemical extracts were tested for toxicity and by comparative chromatography. The collection of Senecio speciosus and Senecio macrocephalus specimens in the Selmar Schonland Herbarium (GRA) was also examined morphologically. Six geographical areas were represented in the combined collections. Analysis of morphological data separated typical Senecio speciosus and Senecio macrocephalus at either end of hybrid index histograms and principal components analysis diagrams. The intermediate populations displayed morphological characters of both Senecio speciosus and Senecio macrocephalus. Some specimens were intermediate between these two species, falling within the range of variation of these species while others fell outside this range. The Brine Shrimp Assay was used to test for toxicity and to investigate the possibility of using toxicity data as a genetic marker in taxonomic studies. As Senecio speciosus extracts were less than 1% toxic and Senecio macrocephalus extracts were at least 95% toxic to the brine shrimps it is suggested that in this case toxicity can be used as a genetic marker. Toxicity can even be described as a good taxonomic character as discontinuity is very sudden and complete. The intermediate plants in the Grahamstown area were at least 92% toxic to the brine shrimps linking them to Senecio macrocephalus. Thin layer and paper chromatography were used as comparative techniques to study the chemical profiles of the specimens. Alkaloids, terpenoids and flavonoids were studied. Thin layer chromatography to separate the alkaloid components of the plant extracts showed Senecio speciosus and Senecio macrocephalus to have distinct chemical profiles suggesting that they are separate species. The intermediate plants- were found to contain chemical compounds matching either or both Senecio speciosus and Senecio macrocephalus suggesting that they may have arisen by hybridisation. In a preliminary investigation Senecio speciosus extracts showed a complete lack of terpenoid compounds whereas extracts from Senecio macrocephalus and the intermediate specimens tested gave a terpenoid colour reaction in the basal spot only. This links the intermediate populations with Senecio macrocephalus. Paper chromatography to separate the flavonoid constituents of the plant extracts also showed typical Senecio speciosus and Senecio macrocephalus to be distinct. The intermediate populations contained flavonoid compounds from one or both of these species. The populations in the Grahamstown area show morphological features close to and in some cases indistinguishable from Senecio speciosus. Chemically these specimens show some similarities with Senecio macrocephalus. In the East London area specimens show a similar mixture of characters but appear morphologically to be closer to Senecio macrocephalus. However, in the Amatole Mountains, despite both species being present in the same locality it appears that no hybridisation has occurred. It is therefore suggested that at some of the localities where the geographical ranges of Senecio speciosus and Senecio macrocephalus overlap in the Eastern Cape Province hybridisation between these two species occurs.
- Full Text: