A range of chromone-2-carboxylic acids has been prepared by condensing suitably substituted 2-hydroxyacetophenones with diethyl oxalate. pK₂ Studies of these acids revealed that 6- or 7-methoxy substituents decreased acidity while the 6-nitro group enhanced acidity; the strongest acid was the 3-chloro derivative, the increase in acidity being attributed to steric inhibition of acid-weakening delocalisation between the carboxyl group and the chromone system. Various chromone-2-carboxamides, derived from acid chloride precursors, were converted to polysubstituted acrylamides by nucleophilic ring-opening with selected amine nucleophiles. The main fragmentation patterns exhibited by these acrylamides were elucidated using a combination of low resolution, high resolution and meta-stable peak analysis, while the effect of substituents on the simultaneous internal rotation involving the carboxamide and enamine moieties were studied using dynamic NMR spectroscopy. Rotational barriers of ca. 67.1 kJmol ̄¹ and ca. 102 kJmol ̄¹ were found for the enamine and amide rotors, respectively. Several synthetic pathways were followed to prepare a series of 2-(N,N-dialkylamino)chromones which were subjected to detailed mass spectral analysis. In addition to substituent-specific fragmentations , the 2-aminochromones appear to fragment via 3 major pathways. The effect of substituents on the internal rotation of the amino moeity was investigated by variable temperature ¹H NMR spectroscopy and the resulting DNMR data was used to calculate the rotational barriers. Examination of the data reveals that the electron-releasing 6- and 7- substituents reduce the C-NMe₂ rotational barrier to ca. 43.5 kJmol ̄¹ , while the nitro analogue has the largest rotational barrier (ca. 46.1 kJmol ̄¹) because of the electron-withdrawing effect of this substituent.

The reaction of salicylaldehyde with various activated alkenes, viz., methyl vinyl ketone, ethyl vinyl ketone, phenyl vinyl sulfone, phenyl vinylsulfonate, acrolein and acrylonitrile, under Baylis-Hillman conditions, has been found to proceed with the chemoselective formation of chromene derivatives. The reaction conditions have been optimised and chromene derivatives have been obtained in isolated yields up to 87 %. The generality of the reaction, using 1,4-diazabicyclo[2.2.2]octane (DABCO), as the catalyst, and a heterogeneous (chloroform-water) solvent system, has been established using a range of salicylaldehyde derivatives,. including 2-hydroxynaphthaldehyde. The formation of chromene derivatives, under these conditions, has been assumed to proceed via an initial, Baylis-Hillman reaction, followed by cyclisation involving intramolecular conjugate addition, and subsequent dehydration. Evidence supporting this sequence has been obtained from the isolation ofBaylis-Hillman products from reactions involving the use of tertbutylclimethylsilyl-protected salicylaldehyde, 4-hydroxybenzaldehyde and tert-butyl acrylate as substrates. The potential of the ''Baylis-Hillman zwitterion" to participate as a donor species in Michael-type addition reactions has been explored and a series of climeric products has been isolated. The Baylis-Hillman methodology has also been successfully extended to the synthesis of sulfurcontaining heterocyclic systems, and a range of 3-substituted thiochromenes has been obtained in moderate yields, using 2,2'-dithiobenzaldehyde and various activated alkenes in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as catalyst. The electron-impact mass spectra of selected chromene and thiocbromene derivatives have been investigated permitting comparison of the fragmentation of the oxygen- and sulfur-containing analogues. In a study directed at the synthesis of potential HIV -1 protease inhibitors, chromene- and thiocbromene-containing analogues of the clinically useful drug, ritonavir, have been prepared. Thiochromene and chromene derivatives were converted to the corresponding 3 -carboxylic acids and coupled with a specially prepared, hydroxyethylene dipeptide isostere to afford ritonavir analogues containing cbromene and thiochromene termini in ca. 60% yield.

During neoplastic development cellular requirements for the micronutrients and macronutrients increase dramatically for the primary metabolites, sugar and amino-acids. This concept of increased cellular needs lead to the development of antimetabolites as anticancer agents. Antimetabolites, are structurally similar to that of physiological metabolites, but have the ability to interfere with normal metabolic functioning of the cell that eventually leads to cell death. One such agent used in chemotherapy is 6-thioguanine. Another group of agents that also only recently showed potential for the used in cancer therapy are the Au containing anti-arthritic gold compounds, such as Auranofin. Both these groups, antimetabolites and Au containing compounds have different intracellular targets e.g. DNA(6-Thioguanine) and thioredoxin reductase [Au(I) and Au(III)], respectively. No study thus far has attempted to combine gold to 6-thioguanine nor has it been tested on non-cancerous and cancer cell lines. In this study two novel Au(I) compounds were synthesized i.e. a Au (I) metal 6-thioguanine (EKJC56) compound and Au (I)-phoshine 6-thioguanine (EKJC80A) compound (Figure 1). The cytotoxic effect and selectivity of these novel compounds were determined on several cancerous and normal cell cultures using the MTT assay. The cells were exposed to varying concentrations of these compounds. The novel compounds (EKJC56ST, EKJC56, and EKJC80A) showed higher toxicity towards all the cancerous cell lines tested, while EKJC56ST and EKJC56 showed only slight inhibition of the proliferation of normal cell cultures. These novel compounds proved to be more selective towards the hormone dependent cell line compared to the non-hormonal cell lines. The Au-phoshine compound, EKJC80A were non selective for both cancerous cells and normal cell cultures. The mechanism of action of these compounds were evaluated and showed a higher percentage of induction early apoptosis compared to an untreated control group. These results were supported when the effect of these derivatives were evaluated on the activation of caspase-3 activity, a known marker of early apoptosis. On evaluation of the effect of these compounds on the mitochondrial membrane it was observed that the mitochondrial membrane of the HeLa cell line became hyperpolarized, but did not prove to be statistical significant. No significant changes in cell cycle phases were observed when cell cycle progression was investigated. Due to limited amounts of thioredoxin reductase enzyme an observational study was conducted to determine the possible involvement of the Au(I) side chain of the novel compounds on the functionality of this enzyme. It was observed that these novel Au(I) containing compounds were as effective as Auranofin to inhibit this enzyme at a concentration as low as 0.1ìM. Further enzymatic studies are still required to support the hypothesis. This study can assist in developing new multi-acting chemotherapeutic drugs that may have the potential to effectively and selectively treat cancer and minimize the development of resistance during treatment. / Dissertation (MSc)--University of Pretoria, 2009. / Pharmacology / unrestricted

The butyne, HC≡CCF(CF₃)₂, can be prepared via the dehydro-halogenation of ICH=CHCF(CF₃)₂, the olefin is produced by the ultraviolet irradiation of mixtures of (CF₃)₂CFI and acetylene. Group IV perfluoroalkynyl derivatives (CH₃)[subscript n]M(C≡CR[subscript f])[subscript 4-n] (n = 0 ↦ 3; M = Si, Ge, Sn; R[subscript f] = CF₃> C₂F₅, CF(CF₃)₂) can be prepared by the reaction of XMg C≡CR[subscript f] (X = Br, I) with the appropriate group IV organohalide. Some, but not all, of the combinations of n, M, and R[subscript f] are described. The reaction of CH₃Si[symbol omitted]₃ with IMgC≡CCF₃ produces (CH₃)₂Si(C≡CCF₃)₂. Difluorocarbene from (CH₃)₃SnCF₃ at 150° adds to the C≡C bond of HC≡CR[subscript f] (R[subscript f] = CF₃, C₂F₅, CF(CF₃)₂) and some of the (CH₃)[subscript n]M(C≡CR[subscript f])[subscript 4-n] derivatives to give the corresponding cyclopropenes, [formula omitted] and [formula omitted] respectively. The spectral properties of the group IV perfluoroalkynyl and cyclopropenyl derivatives exhibit several novel trends. The difluorocarbene species from (CH₃)₃SnCF₃ is electrophilic and is in a singlet state in gas phase addition reactions to unsaturated bonds. The carbene adds stereospecifically to both cis- and to trans-butene-2 to give the corresponding isomeric cyclopropanes. The carbene also inserts into the Sn-H bond of (CH₃)₃SnH. The ultraviolet irradiation of mixtures of (CF₃)₂CFI and (CH₃)₃SnSn(CH₃) produces (CH₃) ₃SnCF(CF₃) ₂. A similar reaction involving (CH₃)₃SnSn(CH₃)₃ and CF₂=CFI produces (CH₃)₃SnCF=CF₂. None of the derivatives, (CH₃)₃SnR[subscript f] (R[subscript f] = C₂F₅, CF(CF₃)₂, CF=CF₂) , produces a carbene upon pyrolysis. Bis(trifluoromethyl)diazomethane reacts with HC≡CCF₃ and with CF₃C≡CCF₃ at ca. 150° to give a mixture of the corresponding isopyrazole, [formula omitted], and cyclopropene, [formula omitted]. Similar reactions of the diazo compound with (CH₃)₃MC≡CCF₃ (M = Ge, Sn) produce [formula omitted] derivatives. The reaction of bis(trifluoromethyl)diazirine and (CH₃)₃GeC=CCF₃ also produces the cyclopropene. The diazo compound inserts C(CF₃)₂ into the M-H bonds of (CH₃)₃SnH and (CH₃)₂AsH and produces (CH₃ )₂AsCF(CF₃) ₂H and (CH₃)₂AsCF=CF₂ upon reaction with (CH₃)₂AsAs(CH₃)₂. The diazo compound fails to react however, with either (CH₃)₃MH (M = Si, Ge), (CH₃)₃GeBr, or (CH₃)₃ GeGe(CH₃ )₃. The Mössbauer spectra of the compounds (CH₃)₃SnR[subscript f] reveal that the quadrupole splitting in the Sn nucleus increases in the order R[subscript f] = CFH₂ < CF₂H < CF₃ ≲ CH(CF₃)₂ < C₂F₅ < CF(CF₃)₂ which indicates the order of increasing electronegativity of the R[subscript f] groups. The order of electronegativity, CF₃ < C₂F₃ < CF(CF₃)₂, is also supported by n.m.r. studies of the compounds HC≡CR[subscript f] and [formula omitted]. As an Appendix the stereochemistry of the olefins produced by the ultraviolet irradiation of mixtures of R[subscript f]I (R[subscript f] = CF₃, C₂F₅, CF(CF₃)₂) and acetylene is described. Predominantly trans addition takes place. / Science, Faculty of / Chemistry, Department of / Graduate

The objectives of the thesis are to describe financial derivatives in a theoretical way and the situations in which they can be applied. How multinational corporations can take advantage of them in different kind of activities. Thesis consist of three chapters. In first chapter there are considered opportunities and threats for a domestic company to expand its activities abroad. It includes the consideration of which necessary activities must be taken prior to the expansion and which most important analysis must be carried out. Finally there is presented the way of dealing with a risk of currency fluctuations and the analysis of exposures that a multinational corporation must face. The second chapter includes a theoretical description and pricing of various types of financial derivatives. It is divided into section of options, futures with forward and swaps. All derivatives type is considered as a tool for hedging and speculations. There are also presented possible outcomes of using derivatives in situations when a market is not in equilibrium and arbitrage possibilities exist. In the third chapter a practical case of a multinational corporation is used as an expample of Lufthansa Group. There are investigated the types of exposures for running a business that this multinational faces and which types of derivatives are used to deal with them. It is analyzed the value of financial derivatives in that corporation, the internal policy to use them, the prerequisites to apply them and the effect of financial derivatives on a company's profitability and financial position.

Hydroxytyrosol is one of the most powerful known antioxidants. It is a naturally occurring polyphenol, most commonly produced in olive trees, (Olea europaea). The remarkable antioxidant and pharmacological properties of hydroxytyrosol has made it an outstanding compound in the polyphenol family and of great interest to many researchers. Hydroxytyrosol can scavenge free radicals produced during cellular oxidative stress and helps to protect the integrity of cells in living systems. Despite its numerous biological and pharmacological uses, it is found in very low concentration in olive oil, this limits its availability for biomedical applications. This work reports a novel and effective method for synthesizing hydroxytyrosol from the readily available precursor catechol. The cellular uptake of hydroxytyrosol is slow due to its high hydrophilicity. Therefore, this research aimed at synthesizing less hydrophilic derivatives of hydroxytyrosol by introducing some selected hydrophobic groups (such as alkyl, acyl, …) to its molecular skeleton.

We investigated the effects of angiotensinogen (Ang), angiotensin I (Ang I), and angiotensin II (Ang II) on the fluidity of phosphatidylcholine vesicles. Changes in fluidity were assessed by changes in anisotopy values calculated from fluorescence polarization measurements. All three compounds produced an increase in membrane fluidity when localized inside the phosphatidylcholine vesicles. When placed outside the vesicles. Ang II increased bilayer rigidity (decreased fluidity), whereas Ang and Ang I produced no effect. These results suggest the possibility that these peptides may alter the fluidity of cell membranes by a direct action on the phospholipid bilayer, which may in turn interfere with receptor-mediated effects.

No description available.

<p> The methylation of three isomeric hexasulphur diimides under basic conditions has been investigated. Both mono- and dimethylated products have been obtained from the 1, 5- and 1,4-hexasulphur diimides. The anion formed from the 1,3 isomer was found to undergo decomposition, the major products being polysulphides and N-methyl heptasulphur imide. The usefulness of proton NMR, mass spectra, and infrared spectra in conjunction with these compounds has been considered.</p> / Thesis / Master of Science (MSc)

No / A series of eleven alpha-aminoacyl stabilised phosphorus ylides 9-19 have been prepared by condensation of N-alkoxycarbonyl protected amino acids with Ph3P=CHCO2Et using a carbodiimide peptide coupling reagent. Upon ash vacuum pyrolysis at 600 degreesC, these undergo extrusion of Ph3PO to give the corresponding, alpha,beta-acetylenic gamma-amino esters 21-29, 33 and 34 in moderate yield. In two cases the terminal alkynes 30 and 31 are also formed. The beta-aminoacyl ylide 20 from beta-alanine similarly gives the alpha,beta-acetylenic delta-amino ester 35 upon pyrolysis. Regioselective addition of HBr to the triple bond of one acetylenic ester 25 was observed giving a mixture of E and Z alpha-bromoacrylates 36. Hydrogenation of the N-Cbz acetylenic esters 21-23 and 33 results in N-deprotection and hydrogenation of the triple bond to afford the chiral GABA analogues 37-40 in 70 --> 95% ee as determined by F-19 NMR of their Mosher amides. Fully assigned C-13 NMR spectra of all the ylides and acetylenic ester derivatives are presented.