Marrubiin and the other two diterpenoids, compounds X and Y, which had previously been isolated from Leonotus leonurus have been reinvestigated. Although the structure for marrubiin is well known its stereochemistry has been the subject of protracted discussion and is by no means secure except at C₅ and C₁₀ . N.M.R. spectral evidence showed that the lactone ring was cis-fused and β-orientated. Dehydration experiments carried out by previous workers were repeated, in order to resolve the residual uncertainty regarding the stereochemistry at C₉, an attempt was made to prepare iodoacetyl marrubic acid for X-ray crystallographic studies. Compound Y, C₂₀H₂₈0₃, a triply-unsaturated compound was shown by spectral studies to contain a furan ring and an α,β- unsaturated keto-group. It possesses a hydroxyl group incapable of acetylation, but readily removed by alkali and dehydrating agents to yield a tetraunsaturated compound, anhydro~Y; the hydroxyl is thus tertiary, Isolation of 1:2:5-trimethylnaphthalene on dehydrogenation indicated a relationship with the labdane diterpene group and supported the C₂₀ formula, The position of the α,β-unsaturated keto-group was resolved by interpretation of the ultraviolet spectra of degradation products and also by isolation of 1:2:3:5- trimethylnaphthalene on dehydrogenation of a suitable grignard product, The presence of a β-substituted furan was further indicated by colour reactions and confirmed by mass and n.m.r. spectra. The skeleton of compound Y is correlated with marrubiin via "iso-ambreinolide " and its stereochemistry is discussed. Further stereochemical assignments are postulated from the study of the n.m.r. spectra. Compound X, C₂₀H₂₈0₅, was shown by spectral and chemical evidence to be a diterpenoid dilactone containing an ether bridge between C₉ and C₁₃ Isolation of 1:2:5 trimethylnaphthal ene on dehydrogenation showed it to be closely related to marrubiin, This was supported by n.m.r. spectral results. A structure for compound X is proposed and the stereochemistry discussed. The aerial portions of Leonotis leonitis were also extracted and shown to contain a new compound, compound R. Preliminary investigation showed that it was a dilactone containing a furan ring, The n.m.r. spectrum of the compound is discussed.

Chromatographic analyses of crude leaf extracts of Flaveria linearis L. revealed the presence of four acetylenic monothiophenes. Three of these metabolites were purified and structurally characterized by UV, NMR, IR, and GC-MS. Germination, growth, and survival/mortality studies with and without UVA, the activating wavelengths of these metabolites, were conducted with the crude leaf extracts and the purified compounds (taken individually and combined) against selected crop species (lettuce, radish, and carrot). Results suggest that acetylenic metabolites are phytotoxic against lettuce, carrot, and radish, but with variability in response among species. These variations in sensitivity and the allelopathic potential of F. linearis is discussed.

The studies and preliminary screening results reported in this paper developed from an initial interest in what appeared to be mildly toxic qualities of the bulbs of the common daffodil, Narcissus pseudonarcissus, Amaryllidaceae. The literature consulted does not shed much light on the mechanisms of the toxic agent or agents, and there appear to be some inconsistencies in respect to the alkaloids extracted. Part of this may be the result of differences in method of extraction, or perhaps lack of agreement on the identity of the actual plant bulbs used as a source of alkaloids. In regard to the chemical isolation of the alkaloids subsequently studied, the closest attention to the details described in several publications did not produce the results described.

Infectious diarrhoea is the second largest single cause of mortality in children under the age of five globally. Bacteria are responsible for most diarrhoeal episodes especially in developing countries, and progressive increase in antimicrobial resistance has given rise to the need to investigate other sources of therapy such as medicinal plants. Ten plant extracts were analysed for their antimicrobial activities using the agar well diffusion and broth microdilution method. Their phytochemical contents were screened, and their effect on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) was used to assess their antioxidant activities. Their toxicity profiles were evaluated using the XTT Cytotoxicity Assay. Water and methanol extracts of Adansonia digitata v ABSTRACT Infectious diarrhoea is the second largest single cause of mortality in children under the age of five globally. Bacteria are responsible for most diarrhoeal episodes especially in developing countries, and progressive increase in antimicrobial resistance has given rise to the need to investigate other sources of therapy such as medicinal plants. Ten plant extracts were analysed for their antimicrobial activities using the agar well diffusion and broth microdilution method. Their phytochemical contents were screened, and their effect on 1, 1-diphenyl-2-picrylhydrazyl (DPPH) was used to assess their antioxidant activities. Their toxicity profiles were evaluated using the XTT Cytotoxicity Assay. Water and methanol extracts of Adansonia digitata seeds and pulp showed no inhibition against all the test organisms, while water and methanol extracts of A. digitata leaves showed inhibition, with minimum inhibitory concentration (MIC) ranging from 0.39 to 6.25mg/ml. Water and methanol extracts of Garcinia livingstonei and Sclerocarya birrea barks showed good activity against all the test organisms, with MICs between 0.39 and 1.56 mg/ml. Alkaloids, phenols, flavonoids, saponins, tannins, and terpenoids were found in one or more of the plant extracts, and all the plant extracts demonstrated scavenging power against DPPH.The cytotoxicity of extracts of Garcinia livingstonei, and Sclerocarya birrea barks ranged between 105.9 μg/ml and 769.9 μg/ml. The results obtained in this study validate the traditional use of A. digitata leaves, G. livingstonei and S. birrea bark in treating bacteria causing diarrhoea. / Life Sciences / M. Sc. (Life Sciences)

Traditionally, Sceletium tortuosum has been used as a medicine and for social and spiritual purposes. The genus is distributed in the south-western parts of South Africa. This project phytochemically analysed and characterised Sceletium plant extracts and determined if any extract showed anti-malarial properties. Extracts were prepared in ethanol and methanol and various compounds were purified using column chromatography with hexane and ethyl acetate as mobile phase. The structure of isolated compounds, including mesembrine, pinitol, sucrose, mesembrenone and obtusalin, was confirmed using NMR. The Plasmodium Lactate dehydrogenase assay was used to screen all extracts and mesembrine to show that four extracts showed antimalarial activity with activity values ranging between 1.47 μg/ml and 7.32 μg/ml, well below the 10 μg/ml cut off value. The study recommends extracting compounds from fresh plant material and further research as to anti-malarial activity of compounds isolated from Sceletium tortuosum / Life & Consumer Sciences / MSc. (Life Sciences)

The Best M.Phil Thesis in the Faculties of Dentistry, Engineering, Medicine and Science (University of Hong Kong), Li Ka Shing Prize,1995-1997 / published_or_final_version / Chemistry / Master / Master of Philosophy

In most countries, as many as 15 to 25% of the adult population have raised blood pressure. People with hypertension, and even those with mild elevation of blood pressure, are at an increased risk of cardiovascular disease, whether or not the symptoms are present. The risk of serious cardiovascular disease varies greatly among individuals and is also determined by a variety of concomitant risk factors other than the level of blood pressure. Hypertension develops as a result of disturbances of the body's blood pressure regulating system. The biological activity of the renin-angiotensin systems results from a series of specific enzymatic cleavages leading to the generation of angiotensin II, a potent vasoconstrictor. In the treatment of hypertension, inhibition of the angiotensin converting enzyme is established as one modern therapeutic principle. Angiotensin converting enzyme inhibitors act by inhibiting the conversion of angiotensin I to angiotensin II. The in vitro assay, developed by ELBL and WAGNER (1991) for the detection of angiotensin converting enzyme inhibitors in plant extracts was successfully established during this study. Plants used by traditional healers in South Africa for the treatment of high blood pressure were investigated for their antihypertensive properties, utilizing the established angiotensin converting enzyme assay. Twenty plants were investigated for their angiotensin converting enzyme inhibitory activity. The highest inhibition (97%) was obtained by Adenopodia spicata leaves. A further seven plants exhibited an inhibition greater than 70% and five more over 50%. Plants exhibiting inhibition levels greater than 50% were further tested for the presence of tannins in order to eliminate possible false positives. The leaves of Tulbaghia violacea were chosen for bioassay-guided fractionation in an attempt to isolate the active compound(s). Serial extractions were made of ground Tulbaghia violacea leaves using polar to non-polar solvents to establish the solvent giving optimum extraction of the active compound(s). Distilled H2O was selected as the extractant and a bulk extract was performed on 0.7 kg ground leaves. The extracted residue was partitioned against butanol, fractionated using cation exchange resin chromatography, Sephadex ® LH-20 and high performance liquid chromatography. Fractions collected after each purification step were assayed using the angiotensin converting enzyme assay. Fractions exhibiting high levels of angiotensin converting enzyme inhibition were selected for further purification. The active fraction from the final high performance liquid chromatography step used in this study requires further attention in order to purify and identify the active compound(s). The chromatographic and chemical properties of the compound(s) present in the isolated active fraction are discussed. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1998.

This project is focused on the synthesis and biological activity of aloin and derivatives. Aloin is a C-glucoside anthrone that is found in Aloe marlothii, a common Southern African plant used in traditional medicine. Aloin was isolated from A. marlothii, employing a selective chelation isolation procedure. This compound is known to have numerous biologically active properties, and can be used as a laxative, an anti-bacterial agent, an anti-oxidant, and as a cytotoxic drug against breast and ovarian tumour cell lines. More relevant to this research investigation, was the reported anti-inflammatory activity of aloin. Specifically, the inhibitory activity of aloin on matrix metalloproteinases, which when excessively secreted, can lead to the development of osteoarthritis and cancer metastasis. Aloin has also been reported to have antiplasmodial activity, which was also investigated. Aloin was synthetically transformed into several derivatives, which could be potentially useful medicinal compounds. The choice of derivatives to be made was based upon (i) known biologically active compounds (e.g. aloe-emodin) and (ii) interesting biologically active functional groups (e.g. amines). These aloin derivatives include aloe-emodin, rheinal, rhein and three amine derivatives. Homonataloin, an aloin-analogue, which was also isolated from A. marlothii, was synthetically transformed into nataloe-emodin. These two compounds serve as aloin structural analogues for the biological testing. Aloin and derivatives were characterised using NMR, HR-MS, UV and IR, which allowed for their unambiguous structural elucidation. Aloin and derivatives were all tested for (i) possible inhibition towards MMP-2 and MMP-9, which are the two most common MMPs in the blood, and (ii) antiplasmodial activity against chloroquine sensitive Plasmodium falciparum parasites. Doxycycline, a clinical tetracycline drug, was used as a reference compound for the biological assays, since it shares many common structural features with aloin and derivatives. 11-(Piperidin-1-yl)chrysophanol and 11-(morpholin-1-yl)chrysophanol proved to be the most potent selective MMP-2 inhibitors. 11-(Piperidin-1-yl)chrysophanol was also found to be the most potent against P. falciparum parasite, along with 11-(pyrrolidin-1-yl)chrysophanol. Aloin has been shown to be a cheap, easily obtainable lead compound that could facilitate the production of a range of powerful medicinal drugs. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2008.

Ledebouria ovatifolia (Bak.) lessop, Clivia caulescens R.A.Dyer and Haemanthus pauculifolius Snijman & Van Wyk were the three species investigated in this work. Ledebouria ovatifolia belongs to the family Hyacinthaceae (Liliaceae sensu lato) and, to date, the chemical composition of this species has not been investigated. Members of this family are widely distributed, but are particularly well represented in Southern Africa. The Ledebouria genus was formerly classified as part of the Scilla genus from which a large number of naturally occurring oxygen heterocycles known as homoisoflavonoids have been isolated. In this work the bulbs of L. ovatifolia were investigated and two compounds were isolated. These were the homoisoflavonoid, 5,7-dihydroxy-3-(4'-hydroxybenzyl)-4-chromanone and the chalcone, 6',2'-dimethoxy-4,4'dihydroxychalcone, both of which are known naturally occurring compounds. Clivia caulescens and Haemanthus pauculifolius are both members of the Amaryllidaceae family. The plants of the Amaryllidaceae family form a large group of over sixty genera, which are concentrated mainly in Southern Africa. Plants from this family have been extensively used in traditional medicines and many have pharmacological properties. The compounds responsible for most of these effects are a group of isoquinoline alkaloids, which are found almost exclusively in plants belonging to this family. The alkaloids isolated from plants belonging to this group are known to cause poisoning in low doses and can cause excessive salivation and diarrhoea. Higher doses of the active compounds can cause CNS depression and large enough doses can prove fatal. Although many of these alkaloids are harmful to man, some of the unique Amaryllidaceae alkaloids exhibit anti-tumour and anti-viral activities, and are thus potentially beneficial to man. The Clivia genus is endemic to South Africa and the most common species, C. miniata, is used by traditional healers to facilitate childbirth and as a snake bite remedy. In this chemical investigation both the bulbs and the leaves of C. caulescens were investigated. The ethanol extract of the bulbs yielded four alkaloids, hippeastrine, haemanthamine, lycorine and ll-(S)-hydroxyvittatine. The investigation of the leaf extract also yielded lycorine and hippeastrine as well as an additional alkaloid sternbergine. Haemanthus pauculifilius is a recently described member of the Haemanthus genus, which consists of 27 taxa that are restricted to Southern Africa and Namibia. In this chemical investigation the ethanol extract of the bulbs and leaves yielded the common triterpenoid sitosterol as well as two novel 5,11-methanomorphanthridine type alkaloids, montanine hydrochloride and manthidine. / Thesis (M.Sc.)-University of Natal, Durban, 1999.

This work is an account of investigations into the chemistry of one of the members of the Amaryllidacae family, Ammocharis coranica, and one of the members of the Fabaceae family, Sophora velutina. Chapter one is an account of the extractives from the bulbs of Ammocharis coranica. In all, twelve compounds, eight alkaloids and four cycloartane compounds have been isolated of which one alkaloid and one cycloartane compound have not been described previously. Plants belonging to the Amaryllidacae family have been used by traditional healers, especially in Africa, to treat a range of illnesses and diseases. The alkaloids isolated from these plants have been shown to exhibit responses to muscle stimulant, antiviral, antifungal, antiyeast, antimalarial, cytotoxic and antitumoural activities. Ammocharis coranica is used by the Zulu tribe in South Africa to treat any illness believed to be caused by witchcraft. Alkaloids from the three most common types among the isoquinoline group were found in this species. These are lycorine, 1-O-acetyllycorine, hippadine, acetylcaranine, and the novel 1-O- acetyl-9-norpluviine from the lycorine type, 6-α-hydroxypowelline from the crinine type and hamayne and crinamine from the haemanthamine type. Cycloartane compounds have not been reported previously from the Amaryllidaceae family. All four cycloartane compounds had a common side chain, containing an olefinic methylene group at position 24, but differed in their substituents at positions 3 and 4. These compounds were found to be 24-methylenecycloartan-3β-ol, cycloeucalenol, cycloeucalenone and the novel compound 4-methylenepollinastanone. Chapter two is an account of the extractives from the seeds of Sophora velutina. The seeds of other Sophora species have been used in traditional ceremonies by the Indians of the Southwest United States and adjacent Mexico because of their hallucinogenic activity. The seeds of Sophora velutina subsp. zimbabweensis found in Zimbabwe are suspected to have historically been used by the natives for their hallucinogenic properties. These plants have been known to contain several quinolizidine alkaloids, flavonoids and isoflavonoids. One alkaloid, N-methylcytisine and two isoflavones, pseudobaptigenin and calycosin, as well as the common phytosterol, β-sitosterol were isolated from the seeds of this species. N-methylcytisine is a common quinolizidine alkaloid, isolated previously from several Sophora species and pseudobaptigenin and calycosin are well known isoflavones, isolated previously from several species in the Fabaceae. / Thesis (M.Sc.)-University of Natal, Durban, 1999.