Greener methodology for the synthesis of alpha-diazocarbonyl compounds and a novel approach to dioxinone derivatives

This thesis outlines a more environmentally benign approach to diazo transfer, and the investigation of the reactivity of -diazocarbonyl compounds when subjected to transition metal and lanthanide catalysis. Extensive studies were carried out to find the optimum conditions for a greener diazo transfer methodology, and this was also applied to a continuous process for the synthesis of -diazo--ketoesters. The first chapter includes a literature review of the synthesis and subsequent reactivity of -diazocarbonyl compounds. An overview of the applications of flow chemistry for the synthesis of hazardous intermediates is also included. The applications of lanthanide catalysts in organic synthesis is also discussed. The second chapter outlines the extensive studies undertaken to determine the optimum conditions for a greener diazo transfer methodology, including base and solvent studies. Use of water as a viable solvent for diazo transfer was successfully investigated. Diazo transfer to a range of -diazo--ketoesters was achieved using 5 mol% triethylamine or DMAP in water with high conversions. Polystyrene-supported benzenesulfonyl azide as an alternative diazo transfer reagent was also explored, as well as investigations into cheaper generation of this safer reagent. This polymer-supported benzenesulfonyl azide was used with 25 mol% of base in water to achieve successful diazo transfer to a range of -diazo--ketoesters. The third chapter describes the application of the new methodology developed in Chapter 2 to a continuous processing approach. Various excellent conditions were identified for both batch and flow reactions. A series of -diazo--ketoesters were synthesised with excellent conversions using 25 mol% triethylamine in 90:10 acetone water using flow chemistry. Successful diazo transfer was also achieved using a polymer-supported benzenesulfonyl azide in water under flow conditions. The fourth chapter discusses the reactivity of -diazo--ketoesters under transition metal and lanthanide catalysis. This chapter describes the synthesis of a range of -ketoesters via transesterification, which were used to synthesise a range of novel -diazo--ketoesters that were used in subsequent decomposition reactions. A novel route to dioxinones via rhodium(II) catalysis is reported. Attempted OH and SH insertion reactions in the presence of various lanthanide(II) catalysts are outlined, leading to some unexpected and interesting rearrangement products. The experimental details, including spectroscopic and analytical data for all compounds prepared, are reported at the end of each chapter.

New N-acylamino acids and derivatives from renewable fatty acids: gelation of hydrocarbons and thermal properties

This work reports the synthesis of new fatty N-acylamino acids and N-acylamino esters from the C16:0, C18:0, C18:1, and C18:1(OH) fatty acid families and demonstrates the activity of these compounds as organogel agents. Compounds were heated and dissolved in various solvents (n-hexane, toluene, and gasoline). Only saturated C16:0 and C18:0 derived from alanine were able to form gels in toluene, and saturated C16:0 derived from phenylalanine showed gelation in n-hexane. This is the first evidence that fatty N-acylamino esters and N-acylamino acid derivatives of l-serine and fatty acids C16:0, C18:0, and C18:1 are able to form gels with hexane. This observation confirms the importance of the hydroxyl group in the segment derivative of l-serine in forming good gels.

Diketopyrrolopyrrole derivatives for bulk heterojunction and dye sensitised solar cells

This thesis describes the synthesis and characterisation of a series of molecules for use in bulk heterojunction and dye sensitised solar cells. The target molecules were based on a central diketopyrrolopyrrole subunit. Molecules based on diketopyrrolopyrrole have a conjugated structure, allowing for π-π interaction. Diketopyrrolopyrrole molecules also have relatively low lying HOMO and LUMO levels and high absorption coefficients and exhibit efficient charge transport properties. Furthermore, their electron withdrawing properties have warranted their use as promising organic photovoltaic materials. A number of molecules were successfully synthesised and sent to collaborators for testing in organic photovoltaic devices and development of this series of molecules continues to be of interest within the research group.

Genetic diversity of stay-green sorghums and their derivatives revealed by microsatellites

The genetic variability of 28 sorghum genotypes of known senescence phenotype was investigated using 66 SSR markers well-distributed across the sorghum genome. The genotypes of a number of lines from breeding programmes for stay-green were also determined. This included lines selected phenotypically for stay-green and also RSG 03123, a marker-assisted backcross progeny of R16 (recurrent parent) and B35 (stay-green donor). A total of 419 alleles were detected with a mean of 6.2 per locus. The number of alleles ranged from one for Xtxp94 to 14 for Xtxp88. Chromosome SBI-10 had the highest mean number of alleles (8.33), while SBI-05 had the lowest (4.17). The PIC values obtained ranged from zero to 0.89 in Xtxp94 and Xtxp88, respectively, with a mean of 0.68. On a chromosome basis, mean PIC values were highest in SBI-10 (0.81) and lowest in SBI-05 (0.53). Most of the alleles from B35 in RSG 03123 were found on chromosomes SBI-01, SBI-02 and SBI-03, confirming the successful introgression of quantitative trait loci associated with stay-green from B35 into the senescent background R16. However, the alternative stay-green genetic sources were found to be distinct based on either all the SSRs employed or using only those associated with the stay-green trait in B35. Therefore, the physiological and biochemical basis of each stay-green source should be evaluated in order to enhance the understanding of the functioning of the trait in the various backgrounds. These genetic sources of stay-green could provide a valuable resource for improving this trait in sorghum breeding programmes.

Catalytic asymmetric synthesis of alfa,alfa-disubstituted alfa-thio- and alfa-amino acid derivatives

449 p.

Antiangiogenic potential of yogurts added with extracts rich in apigenin derivatives

Angiogenesis is a biological process through which there is the formation of new blood vessels from preexisting ones [I]. However, in pathological cases, the abnormal growth of new blood vessels promotes the development of various diseases including cancer [2) through the production of atypically large amounts of angiogenesis factors, e.g. the vascular endothelial growth factor (VEGF) [3]. The plant secondary metabolites have been the subject of several studies to evaluate their benefits to human health. In particular, the phenolic compounds have high potential for use in the food industry, including the development of functional foods. Among these, apigenin has been associated with chemopreventive effects related to cancer [4]. In fact, chemoprevention is a present-day concept and contemplates the use of medicines, biological compounds or nutrients as an intervention strategy of cancer prevention. In this work, an Arenaria montana L hydroethanolic extract was prepared and after characterization by HPLC-DAD-ESI/MS showed to be rich in apigenin derivatives. Furthermore, it exhibited ability to inhibit the phosphorylation of VEGFR-2 (vascular endothelium growth factor receptor) through an enzymatic assay. However, for the major protection of bioactive compounds, the extract was microencapsulated by an atomization/coagulation technique with alginate as the matrix material. Posteriorly, the hydroethanolic extract, in free and microencapsulated forms, was incorporated in yogurts in order to develop a novel chemopreventer food in relation to the angiogenesis process. The functionalized yogurts with A. montana extracts (free and microencapsulated) showed a nutritional value similar to the used control (yogurt without extract); however, the samples enriched with extracts revealed added-value regarding the VEGFR-2 phosphorylation inhibition ability. This effect was more effectively preserved over time in the samples functionalized with the protected extract. Overall, this work contributes to the valorization of plants rich in flavonoids, exploring its antiangiogenic potential with VEGFR-2 as target. Moreover, the atomization/coagulation technique allowed the production of viable microspheres enriched with the plant extract. The microspheres were effectively incorporated into yogurts, protecting the extract thus envisaging the development of novel functional foods with chemopreventive effects.

Pricing derivatives with stochastic volatility

This Ph.D. thesis contains 4 essays in mathematical finance with a focus on pricing Asian option (Chapter 4), pricing futures and futures option (Chapter 5 and Chapter 6) and time dependent volatility in futures option (Chapter 7). In Chapter 4, the applicability of the Albrecher et al.(2005)'s comonotonicity approach was investigated in the context of various benchmark models for equities and com- modities. Instead of classical Levy models as in Albrecher et al.(2005), the focus is the Heston stochastic volatility model, the constant elasticity of variance (CEV) model and the Schwartz (1997) two-factor model. It is shown that the method delivers rather tight upper bounds for the prices of Asian Options in these models and as a by-product delivers super-hedging strategies which can be easily implemented. In Chapter 5, two types of three-factor models were studied to give the value of com- modities futures contracts, which allow volatility to be stochastic. Both these two models have closed-form solutions for futures contracts price. However, it is shown that Model 2 is better than Model 1 theoretically and also performs very well empiri- cally. Moreover, Model 2 can easily be implemented in practice. In comparison to the Schwartz (1997) two-factor model, it is shown that Model 2 has its unique advantages; hence, it is also a good choice to price the value of commodity futures contracts. Fur- thermore, if these two models are used at the same time, a more accurate price for commodity futures contracts can be obtained in most situations. In Chapter 6, the applicability of the asymptotic approach developed in Fouque et al.(2000b) was investigated for pricing commodity futures options in a Schwartz (1997) multi-factor model, featuring both stochastic convenience yield and stochastic volatility. It is shown that the zero-order term in the expansion coincides with the Schwartz (1997) two-factor term, with averaged volatility, and an explicit expression for the first-order correction term is provided. With empirical data from the natural gas futures market, it is also demonstrated that a significantly better calibration can be achieved by using the correction term as compared to the standard Schwartz (1997) two-factor expression, at virtually no extra effort. In Chapter 7, a new pricing formula is derived for futures options in the Schwartz (1997) two-factor model with time dependent spot volatility. The pricing formula can also be used to find the result of the time dependent spot volatility with futures options prices in the market. Furthermore, the limitations of the method that is used to find the time dependent spot volatility will be explained, and it is also shown how to make sure of its accuracy.

Determination of the cytotoxic capacity of organotin compounds derivatives from salicylidene benzoylhidrazone

The successful application of metal complexes in the treatment of many diseases, including cancer, is a rapidly expanding area in biomedical chemistry and research. Organotin compounds studies show the versatility and the attractive features of these molecules. In the same manner, has been reported the development of new compounds derivative from bezoylhidrazones, which possess the azomethine fragment (-N = CH-), key pillar for designing new drugs with biological activity. Based on the above, we are interested in to synthesize four tin compounds derivatives from benzoylhidrazones, and the evaluation of their cytotoxic capacity. Conclusions and contribution: In this research work, we reported four new tin compounds derivatives from bezoylhidrazones, which were characterized by spectroscopic and spectrometric techniques and X-ray diffraction In the same manner, cytotoxic ability of each compound was studied and reported and compared with metaled base drugs like cisplatin and carboplatin. Also, in some cases it was possible to use their luminescent ability to study their intracellular behavior.

Aqueous solubilities of five N-(diethylaminothiocarbonyl)benzimido derivatives at T = 298.15 K

N-(diethylaminothiocarbonyl)benzimido derivatives are polar multifunctional substances. A set of these compounds was synthesised by successive substitution on the enamine side, resulting in similar substances with different polarities, providing a set of model compounds with respect to the study of substituent effects on physico-chemical properties. Experimental aqueous solubility data, at T = 298.15 K, of N-(diethylaminothiocarbonyl)benzamidine, PhCNH2NCSNEt2 (1),N-(diethylaminothiocarbonyl)-N'-phenylbenzamidine, PhCNHPhNCSNEt2 (2), N-(diethylaminothiocarbonyl)-N'-monoethylbenzamidine, PhCNHEtNCSNEt2 (3), N-(diethylaminothiocarbonyl)-N',N'-diethylbenzamidine, PhCNEt2NCSNEt2 (4), and N-(diethylaminothiocarbonyl)benzimido ethylester, PhCOEtNCSNEt2 (5) were measured at T = 298.15 K. The obtained data are supplemented by COSMO-RS aqueous solubility predictions as well as other environmentally important partition coefficients. This information is shown in a two-dimensional chemical space diagram, providing indications about the compartment into which the bulk of the compounds is likely to concentrate. The expected quality of COSMO-RS predictions for this type of screening exercise is illustrated on a set of pesticides with established thermophysical property data.

Evaluation of anti-inflammatory activity of derivatives from aerial parts of Baccharis uncinella

Context: Species of Baccharis exhibit antibiotic, antiseptic, and wound-healing properties, and have been used in the traditional medicine of South America for the treatment of inflammation, headaches, diabetes, and hepatobiliary disorders.Objective: To investigate the anti-inflammatory activity of organic phases from EtOH extract of the aerial parts of Baccharis uncinella DC (Asteraceae).Materials and methods: The crude EtOH extract from the aerial parts of B. uncinella was subjected to partition procedures and the corresponding CH(2)Cl(2) and EtOAc phases were subjected to several chromatographic separation procedures. Thus, these phases and their purified compounds were assayed for evaluation of anti-inflammatory activity.Results: The CH(2)Cl(2) phase from EtOH extract from B. uncinella contained two triterpenoids (oleanolic and ursolic acids) and one flavonoid (pectolinaringenin), whereas the respective EtOAc phase showed to be composed mainly by two phenylpropanoid derivatives (caffeic and ferulic acids). The CH(2)Cl(2) and EtOAc phases as well as their isolated compounds exhibited anti-inflammatory effects against inflammatory reactions induced by phospholipase A2 (from Crotalus durissus terrificus venom) and by carrageenan.Discussion and conclusion: The results suggested that the components obtained from partition phases of EtOH extract of B. uncinella could represent lead molecules for the development of anti-inflammatory agents. Additionally, the results confirmed the use of Baccharis genus in the traditional medicine of South America for the treatment of inflammation and other heath disorders. To date, the present work describes for the first time the anti-inflammatory effects of compounds isolated from B. uncinella.

Charged pullulan derivatives for the development of nanocarriers by polyelectrolyte complexation

Pullulan, a neutral polysaccharide, was chemically modified in order to obtain two charged derivatives: reaction with SO3(.)DMF complex afforded a sulfate derivative (SP), while reaction with glycidyltrimethylammonium chloride gave a quaternary ammonium salt (AP). The presence of the charged groups was confirmed by FTIR. Assessment of the positions where the reaction took place was based on (1)H- and (13)C NMR (COSY, HSQC-TOCSY, HSQC-DEPT, and HMBC) experiments. Estimation of the degree of substitution (DS) was made from elemental analysis data, and further confirmed by NMR peak areas in the case of AP. These new derivatives showed the capability to condense with each other, forming nanoparticles with the ability to associate a model protein (BSA) and displaying adequate size for drug delivery applications, therefore making them good candidates for the production of pullulan-based nanocarriers by polyelectrolyte complexation.

Reduction of 1,2-dicarbonyl compounds and of their N-phenylimine derivatives by sodium cyanide under aprotic conditions

Some aromatic 1,2-dicarbonyl compounds, i.e. 9,10-phenanthrenequinone, acenaphthenequinone and benzil, and their corresponding N-phenyl monoimines, have been reduced, using dry acetonitrile as the solvent, in the presence of sodium cyanide as a reducing agent. Comparative potentiostatic preparative-scale electrolysis is described.

Synthesis and antibacterial profile of novel azomethine derivatives of β-phenylacrolein moiety

Purpose: To develop some novel molecules effective against antibiotic-resistant bacterial infections. Methods: A series of azomethines (SB-1 to SB-6) were synthesized from β-phenyl acrolein moiety. The structures of the synthesized compounds were confirmed on the basis of their UV ultra-violet (UV) spectroscopy (λmax: 200 - 400 nm), Fourier transform infra-red (FTIR, vibrational frequency: 500-4000 cm-1), 1H nuclear magnetic resonance (NMR, chemical shift: 0 - 10 ppm), 13C NMR (chemical shift: 0 - 200 ppm), mass spectrometry (m/z values: 0 - 500) and carbon hydrogen nitrogen (CHN) elemental analysis. The new compounds were screened for antibacterial activity by test-tube dilution and disc diffusion methods using gentamicin as reference standard. Results: The structures of azomethine were in full agreement with their spectral data. Among all the synthesized compounds, compounds SB-5 and SB-6 exhibited the highest minimum inhibitory concentration (MIC) of 62.5 μg/mL. At MIC of 250 μg/mL, all compounds SB-1 to SB-6 displayed significant antibacterial activity, compared to gentamycin (p < 0.05). SB-5 and SB-6 were active against S. aureus, P. aeruginosa and K. pneumoniae; SB-3 was active against B. subtilis and S. aureus. SB-4 was active against P. aeruginosa and S. aureus while SB-1 and SB-2 were active against S. aureus. Conclusion: The synthesized compounds possess antibacterial activities compared to those of gentamycin.

Corrigendum to “The envelope theorem for multiobjective convex programming via contingent derivatives” [J. Math. Anal. Appl. 372 (1) (2010) 197–207]

The aim of this note is to formulate an envelope theorem for vector convex programs. This version corrects an earlier work, “The envelope theorem for multiobjective convex programming via contingent derivatives” by Jiménez Guerra et al. (2010) [3]. We first propose a necessary and sufficient condition allowing to restate the main result proved in the alluded paper. Second, we introduce a new Lagrange multiplier in order to obtain an envelope theorem avoiding the aforementioned error.