Doctor of Philosophy / Fumonisins B1 6 and B3 8 are toxic secondary metabolites of the fungus Fusarium moniliforme that inhibit enzymes of sphingolipid biosynthesis. This dissertation describes work towards the stereocontrolled total synthesis of the fumonisin natural products. The proposed highly convergent strategy allows for the late stage stereocontrolled coupling of the two fragments C1-C10 58 and C11-C20 57 with concomitant installation of the C10 hydroxyl using key boron aldol methodology. A directed hydrogenation installs the final methyl-bearing stereocentre at C12. Syntheses of the left- and right-hand fragments 57 and 58 by means of substrate-based stereocontrol and asymmetric catalytic methods is reported. A completed synthesis of the protected FB3 carbon backbone 59 is achieved in a linear reaction sequence of 14 steps. Tentative assignment of stereogenic centres within 59 was made by analogy to the C4-C20 fragment 190 of fumonisin B3. Synthesis of C4-C20 190 by the coupling of C11-C20 57 with heptaldehyde is also described.

Doctor of Philosophy / Fumonisins B1 6 and B3 8 are toxic secondary metabolites of the fungus Fusarium moniliforme that inhibit enzymes of sphingolipid biosynthesis. This dissertation describes work towards the stereocontrolled total synthesis of the fumonisin natural products. The proposed highly convergent strategy allows for the late stage stereocontrolled coupling of the two fragments C1-C10 58 and C11-C20 57 with concomitant installation of the C10 hydroxyl using key boron aldol methodology. A directed hydrogenation installs the final methyl-bearing stereocentre at C12. Syntheses of the left- and right-hand fragments 57 and 58 by means of substrate-based stereocontrol and asymmetric catalytic methods is reported. A completed synthesis of the protected FB3 carbon backbone 59 is achieved in a linear reaction sequence of 14 steps. Tentative assignment of stereogenic centres within 59 was made by analogy to the C4-C20 fragment 190 of fumonisin B3. Synthesis of C4-C20 190 by the coupling of C11-C20 57 with heptaldehyde is also described.

Thesis (Ph. D.)--University of Sydney, 2004. / Title from title screen (viewed April 6, 2009). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the School of Chemistry, Faculty of Science. Degree awarded 2004; thesis submitted 2003. Also available in print form.

The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on January 19, 2010) Thesis advisor: Dr. Marcia Shannon Includes bibliographical references.

Fumonisins, mycotoxins produced by the fungus, Fusarium moniliforme, which grows on maize, are a major worldwide agricultural problem. Consumption of contaminated maize feeds causes a wide variety of toxic effects in animals depending on the species of animal. In humans, high concentrations of fumonisins have been shown to correlate with increased incidence of oesophageal cancer (OC). Most analyses for fumonisins are done using high performance liquid chromatography (HPLC) which requires time-consuming extraction and clean-up prior to preparation of a fluorescent derivative. Enzyme-linked immunosorbent assays (ELISA), which are sensitive and specific, are a viable alternative but commercially available antibodies and kits are extremely expensive. Polyclonal antibodies against fumonisin B, (FB,) were raised in chickens and rabbits; all animals produced antibodies from week 2 onwards, the highest titre was at week 8 from one of the chickens. Cross-reactivities with FB, analogues were checked. A sensitive, quantitative competitive indirect ELISA (CI-ELISA) was developed and optimised; range 0.2 to 20 ng/ml (in buffer), detection limit 0.2 nglml (in buffer), intra-assay coefficient of variation (CV) was 5.33 % and inter-assay 7.04%. This method was adapted to analyse human plasma and urine samples. After removal of proteins by boiling, the range of recoveries of FBI were 94.7% toI12.4% at 4 ng/ml; and 94.6% to 108.7% at 8 ng/ml. Blood and urine samples from patients with OC (40 plasma, 17 urine), controls (21 plasma, 12 urine) and patients with other forms of cancer (20 plasma, 10 urine) were collected from hospitals in the Durban Metropolitan area and analysed for fumonisins. Detectable levels (>0.4 nglml) were found in 86.9% of plasma samples and 94.9% of urine samples. Statistical evaluation showed a highly significant difference between plasma results for OC and controls (p<0.000 1) but no significant difference between the urine results. Comparison of other forms of cancer and controls showed no significant differences for either the plasma or the urine samples. However, there was a highly significant difference between the OC and other forms of cancer results for both plasma (p<0.005) and urine (p<0.05) samples. Some samples (9 plasma, 8 urine) were checked by HPLC. For plasma samples there was correlation between the ELISA and HPLC methods (r = 0.656, p<0.005) but not for urine samples.

Thesis (MScAgric)--University of Stellenbosch, 2008. / Bibliography. Also available via the Internet.

Thesis (M.Sc.(Chemistry))--University of Pretoria, 2001. / Includes abstracts in English and Afrikaans. Includes bibliographical references.

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2007. / Title from title screen (site viewed July 10, 2007). PDF text: 115 p. : ill. UMI publication number: AAT 3252836. Includes bibliographical references. Also available in microfilm and microfiche formats.

Submitted in partial fulfillment of the requirements for the degree of Doctor of Technology: Clinical Technology, Durban Institute of Technology, 2005. / Fumonisin B1 (FB1) and ochratoxin A (OTA) represent examples of mycotoxins of greatest public health and agro-economic significance. They exert adverse effects on humans, animals and crops that result in illnesses and economic losses. Fumonisin B1 are cancerpromoting metabolites of Fusarium proliferatum and F verticillioides, (formerly moniliforme), and are implicated in oesophageal cancer. Ochratoxins are metabolites of both Aspergillus and Penicillium species. These compounds are known for their nephrotoxic effects in all animal species and may promote tumours in humans. In man OTA exhibits unusual toxicokinetics, with a half-life in blood of 840 h (35 days) after oral ingestion. Although much is known regarding the toxicology of these toxins, little is known of the effects of these toxins on the immune system. The aim of this study was to determine and compare the immunornodulating effects of FB1 and OTA in human carcinoma. Initial experiments involved isolating lymphocytes and neutrophils from healthy volunteers. The isolated cells were exposed to either FB1 or OTA on a dose and time dependent level and LD50 of the toxins was determined. Thereafter, challenge tests were performed, whereby lymphocytes and neutrophils isolated from volunteers, oesophageal cancer patients and breast cancer patients were exposed to the LD50 dose of either FB1 or OTA for the appropriate time. The effect of the toxins was demonstrated by viability studies, light microscopy and electron microscopy. Cytokine receptors (CK, TNF and CSF) were evaluated by immuno-cytochemical methods and the levels of circulating cytokines (IL -1, IL-6, IL-8, IL-10 and TNF-a) were determined using ELISA kits. / D

Preeclampsia is the leading cause of foetal and maternal mortality and morbidity in developing countries. In South Africa, maize is a dietary staple for most black African populations and is susceptible to contamination by mycotoxins such as fumonisin B1 (FB1).Fumonisin B1 is a ubiquitous secondary metabolite of Fusarium fungi produced predominantly by Fusarium verticillioides. This mycotoxin shares structural similarities with the backbone of sphingoid bases (sphinganine and sphingosine) which are substrates for the biosynthesis of complex sphingolipids. The mechanism of FB1 toxicity therefore is centred on the disruption of this process. The aim of the present study was to elucidate the possible causal link between FB1 and preeclampsia. Following ethical approval, 20 normotensive and 20 preeclamptic patients were recruited into the study. Blood and placental tissue were collected and processed for further analysis. The presence of FB1 was verified using standard immunohistochemical and electrophoretic techniques. The levels of FB1 and sphingolipids were quantified using high performance liquid chromatography (HPLC). Western blotting was conducted to confirm the presence of FB1 in the serum. Placental tissue apoptosis was evaluated using Hoechst staining and other markers. Lipid peroxidation was measured in serum and placental tissue of both groups. Fumonisin B1 was immunolocalised within the endothelial cells and mesenchymal cells of placentas from both groups, while FB1 was present in cytotrophoblastic cells of preeclamptic patients only. In addition, FB1 concentrations were significantly higher in preeclamptic compared to normotensive serum samples. Sphinganine was significantly elevated in preeclamptic serum samples whilst there was no statistical difference in the sphingosine levels between the groups. Chromatin condensation was higher in the preeclamptic patients. Caspase 3 and Fas were present with greater intensity in preeclamptic samples. The levels of lipid peroxidation were significantly higher in both serum and placental tissue of preeclamptic patients. This study has demonstrated not only the presence of FB1 in the serum and placental tissues of pregnant women but also the potential effects of this mycotoxin in the humans. / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2012.