Monoterpenos di-hidroxilados e hidróxi-nitrogenados 1,2 e 1,3 como ligantes quirais em reação de reformatsky assimétrica

This study describes the use of three (-)-alpha-pinene derivatives, one diol-1,2 [(-)-(1R, 2R, 3S, 5R)-2,6,6-trimethylbicyclo[3.1.1]heptane-2,3-diol 4] and two piridine-hydroxy derivatives [(+)-(1R,2S,3R,5S)-2,6,6-trimethyl-3-(2-pyridinylmethyl)bicyclo[3.1.1]heptan-3-ol 7 and (-)-(1R,2S,3R,5S)-2,6,6-trimethyl-3-[2-(2-pyridinyl) ethyl]bicyclo[3.1.1]heptan-3-ol 8]; one diol-1,3 [(-)-(1S,2R,5S)-2-(1-hydroxy-1-methylethyl)-5-methylcyclohexanol 5] derived from (+)-isopulegol 2 and one diol-1,3 [(+)-(1R,2R,5R)-2-(1-hydroxy-1-methylethyl)-5-methylcyclohexanol 6] derived from (+)-neo-isopulegol 3, as ligands in the asymmetric Reformatsky reaction. The best enantiomeric excess of beta-hydroxy ester obtained in the Reformatsky asymmetric reaction was 18% using ligand 6, and the chemical yield of the reactions was 65% on average.

Stereoselective syntheses of (+)- isoretronecanol and (+)-5-epi-tashiromine via addition of chiral titanium (iv) enolates to cyclic n-acyliminium ions

The stereoselective addition of the titanium (IV) enolates derived from (S)-4-isopropyl-N-4-chlorobutyryl-1,3-thiazolidine-2-thione (8) and from (S)-4-isopropyl-N-4-chloropentanoyl-1,3-thiazolidine-2-thione (9) to N-Boc-2-methoxypyrrolidine (5b) afforded the addition products (+)-10 and (+)-11 in 84% yield in both cases, as 8.6:1 and 10:1 diastereoisomeric mixtures, respectively. A three-step sequence allowed to convert these adducts to (+)-isoretronecanol (1) and (+)-5-epi-tashiromine (2) in 43% and 49% overall yield, respectively.

Síntese de aminoálcoois derivados do D-manitol

Aminoalcohols have found important applications in synthetic and medicinal chemistry, being used as chiral building blocks for the synthesis of many biologically active compounds. This class of compounds has been also used as chiral auxiliaries and ligands in asymmetric synthesis. Due to the importance of aminoalcohols in the treatment of several diseases, such as tuberculosis, the aim of this article is the synthesis and preliminary evaluation against tuberculosis of six aminoalcohols in 5 or 6 steps using D-mannitol as starting material, which is a useful carbohydrate employed in many syntheses.

Reações de organocatálise com aminas quirais: aspectos mecanísticos e aplicações em síntese orgânica

The philosophy of organocatalysis is based on the utilization of organic compounds to catalyze organic transformations without the intervention of metals. This area has attracted much attention of the synthetic chemistry community on the last years, which can be confirmed by the explosion of published papers dealing with this subject. Phosphorus compounds, urea and thiourea derivatives, alkaloids, guanidine derivatives, for example, have already been used as organocatalysts. In this review we have focused on the use of chiral amines as organocatalyst. We have also chosen some outstanding examples to demonstrate the potentiality of this strategy in the synthesis of natural products and biologically active compounds.

Potencialidades e oportunidades na química da sacarose e outros açúcares

Non-renewable biomass, such as coal, oil and natural gas are not only energy sources but also important starting materials for the production of a variety of chemicals ranging from gasoline, diesel oil and fine chemicals. In this regard, carbohydrates, the most abundant class of enantiopure organic compounds, are very suitable for generation of chemicals of great practical value. Their bulk-scale availability associated with low cost make them unique starting materials for organic preparative purpose. They are a most attractive alternative for construction of enantiopure target molecules by asymmetric synthesis. This review addresses, in addition to the use of low molecular weight carbohydrates, issues related to renewable biomass from photosynthesis and alternatives for the production of bulk and fine chemicals.

Evolução biomolecular homoquiral: a origem e a amplificação da quiralidade nas moléculas da vida

The fact that biologically relevant molecules exist only as one of the two enantiomers is a fascinating example of complete symmetry breaking of chirality and has long intrigued our curiosity. The origin of this selective chirality has remained a fundamental enigma with regard to the origin of life since the time of Pasteur, 160 years ago. The symmetry breaking processes, which include autocatalytic crystallization, asymmetric autocatalysis, spontaneous crystallization, adsorption and polymerization of amino acids on mineral surfaces, provide new insights into the origin of biomolecular homochirality.

Catálise assimétrica no Brasil: desenvolvimento e potencialidades para o avanço da indústria química brasileira

The preparation of enantiomerically pure or enriched substances is of fundamental importance to pharmaceutical, food, agrochemical, and cosmetics industries and involves a growing market of hundreds of billions of dollars. However, most chemical processes used for their production are not environmentally friendly because in most cases, stoichiometric amounts of chiral inductors are used and substantial waste is produced. In this context, asymmetric catalysis has emerged as an efficient tool for the synthesis of enantiomerically enriched compounds using chiral catalysts. More specifically, considering the current scenario in the Brazilian chemical industry, especially that of pharmaceuticals, the immediate prospect for the use of synthetic routes developed in Brazil in an enantioselective fashion or even the discovery of new drugs is practically null. Currently, the industrial production of drugs in Brazil is primarily focused on the production of generic drugs and is basically supported by imports of intermediates from China and India. In order to change this panorama and move forward toward the gradual incorporation of genuinely Brazilian synthetic routes, strong incentive policies, especially those related to continuous funding, will be needed. These incentives could be a breakthrough once we establish several research groups working in the area of organic synthesis and on the development and application of chiral organocatalysts and ligands in asymmetric catalysis, thus contributing to boost the development of the Brazilian chemical industry. Considering these circumstances, Brazil can benefit from this opportunity because we have a wide biodiversity and a large pool of natural resources that can be used as starting materials for the production of new chiral catalysts and are creating competence in asymmetric catalysis and related areas. This may decisively contribute to the growth of chemistry in our country.

Ultrafiltration membranes from waste polyethylene terephthalate and additives: synthesis and characterization

The synthesis and characterization of asymmetric ultrafiltration membranes from recycled polyethylene terephthalate (PET) and polyvinylpyrrolidone (PVP) is reported. PET is currently used in many applications, including the manufacture of bottles and tableware. Monomer extraction from waste PET is expensive, and this process has not yet been successfully demonstrated on a viable scale. Hence, any method to recycle or regenerate PET once it has been used is of significant importance from scientific and environmental research viewpoints. Such a process would be a green alternative due to reduced raw monomer consumption and the additional benefit of reduced manufacturing costs. The membranes described here were prepared by a phase-inversion process, which involved casting a solution containing PET, m-cresol as solvent, and polyethylene glycol (PEG) of different molecular weights as additives. The membranes were characterized in terms of pure water permeability (PWP), molecular weight cut-off (MWCO), and flux and membrane morphology. The results show that the addition of PEG with high molecular weights leads to membranes with higher PWP. The presence of additives affects surface roughness and membrane morphology.

AVALIAÇÃO DAS NORMAS DE ENSAIO APLICADAS NA QUANTIFICAÇÃO DE PCBs EM ÓLEO ISOLANTE

Polychlorinated biphenyls (PCBs) were widely used between 1940 and 1970 as an insulating fluid for transformers and capacitors. However, they are bioaccumulative and potentially carcinogenic and, according to the 2001 Stockholm Convention, must be eliminated by 2025. In Brazil, they have been gradually eliminated but contaminated equipment remains. The Brazilian official standard for PCBs content in oil analysis is the ABNT NBR 13882 and there is also the IEC 61619 International Standard, both based on GC-ECD quantification. This work identified the inefficiency of these analytical methods and highlights potential failures which generated discrepancies on quantification of these contaminants. It was observed that the IEC 61619 is superior to ABNT NBR 13882 in analytical criteria, but has problems with the inefficiency of the adsorbent material used in pretreatments for removal of oxidation products from oil where these adsorbents adsorbed some PCBs molecules, causing errors in quantification.

The effect of institutional settings on accounting conservatism – Empirical evidence from the Nordic countries and the transitional economies of Europe

The purpose of the dissertation is to investigate how different institutional settings affect accounting conservatism. These aspects are of interest because prior studies show that accounting quality is influenced not only by accounting standards, but also by incentives from the financial reporting environment. Accounting quality could be defined as the usefulness of financial reporting to investors and other parties in contractual relationships with the firm. In this thesis it is measured by a single, but important attribute, accounting conservatism. Conservatism is understood as asymmetric timeliness of loss and gain recognition. The study examines the role and the users of financial statements, and how changes in both respectively affect accounting conservatism. These two questions are explored in two different research environments, the Nordic countries and the transitional economies of Europe. The results of the dissertation indicate that the degree of accounting conservatism increases the closer the financial statement comes to fulfilling the informational role of financial reporting. Secondly, it is also implied that foreign investors demand conservative accounting numbers in order to mitigate the problem of information asymmetry. Overall, the findings suggest that earnings conservatism is useful and increases the quality of financial information for the purpose of decision-making and contracting. These results are of relevance to managers, investors and other users of financial reporting information, as well as to standard setters.

Application of Computational Fluid Dynamics in Modeling Blood Flow in Human Thoracic Aorta

The aim of this study was to simulate blood flow in thoracic human aorta and understand the role of flow dynamics in the initialization and localization of atherosclerotic plaque in human thoracic aorta. The blood flow dynamics in idealized and realistic models of human thoracic aorta were numerically simulated in three idealized and two realistic thoracic aorta models. The idealized models of thoracic aorta were reconstructed with measurements available from literature, and the realistic models of thoracic aorta were constructed by image processing Computed Tomographic (CT) images. The CT images were made available by South Karelia Central Hospital in Lappeenranta. The reconstruction of thoracic aorta consisted of operations, such as contrast adjustment, image segmentations, and 3D surface rendering. Additional design operations were performed to make the aorta model compatible for the numerical method based computer code. The image processing and design operations were performed with specialized medical image processing software. Pulsatile pressure and velocity boundary conditions were deployed as inlet boundary conditions. The blood flow was assumed homogeneous and incompressible. The blood was assumed to be a Newtonian fluid. The simulations with idealized models of thoracic aorta were carried out with Finite Element Method based computer code, while the simulations with realistic models of thoracic aorta were carried out with Finite Volume Method based computer code. Simulations were carried out for four cardiac cycles. The distribution of flow, pressure and Wall Shear Stress (WSS) observed during the fourth cardiac cycle were extensively analyzed. The aim of carrying out the simulations with idealized model was to get an estimate of flow dynamics in a realistic aorta model. The motive behind the choice of three aorta models with distinct features was to understand the dependence of flow dynamics on aorta anatomy. Highly disturbed and nonuniform distribution of velocity and WSS was observed in aortic arch, near brachiocephalic, left common artery, and left subclavian artery. On the other hand, the WSS profiles at the roots of branches show significant differences with geometry variation of aorta and branches. The comparison of instantaneous WSS profiles revealed that the model with straight branching arteries had relatively lower WSS compared to that in the aorta model with curved branches. In addition to this, significant differences were observed in the spatial and temporal profiles of WSS, flow, and pressure. The study with idealized model was extended to study blood flow in thoracic aorta under the effects of hypertension and hypotension. One of the idealized aorta models was modified along with the boundary conditions to mimic the thoracic aorta under the effects of hypertension and hypotension. The results of simulations with realistic models extracted from CT scans demonstrated more realistic flow dynamics than that in the idealized models. During systole, the velocity in ascending aorta was skewed towards the outer wall of aortic arch. The flow develops secondary flow patterns as it moves downstream towards aortic arch. Unlike idealized models, the distribution of flow was nonplanar and heavily guided by the artery anatomy. Flow cavitation was observed in the aorta model which was imaged giving longer branches. This could not be properly observed in the model with imaging containing a shorter length for aortic branches. The flow circulation was also observed in the inner wall of the aortic arch. However, during the diastole, the flow profiles were almost flat and regular due the acceleration of flow at the inlet. The flow profiles were weakly turbulent during the flow reversal. The complex flow patterns caused a non-uniform distribution of WSS. High WSS was distributed at the junction of branches and aortic arch. Low WSS was distributed at the proximal part of the junction, while intermedium WSS was distributed in the distal part of the junction. The pulsatile nature of the inflow caused oscillating WSS at the branch entry region and inner curvature of aortic arch. Based on the WSS distribution in the realistic model, one of the aorta models was altered to induce artificial atherosclerotic plaque at the branch entry region and inner curvature of aortic arch. Atherosclerotic plaque causing 50% blockage of lumen was introduced in brachiocephalic artery, common carotid artery, left subclavian artery, and aortic arch. The aim of this part of the study was first to study the effect of stenosis on flow and WSS distribution, understand the effect of shape of atherosclerotic plaque on flow and WSS distribution, and finally to investigate the effect of lumen blockage severity on flow and WSS distributions. The results revealed that the distribution of WSS is significantly affected by plaque with mere 50% stenosis. The asymmetric shape of stenosis causes higher WSS in branching arteries than in the cases with symmetric plaque. The flow dynamics within thoracic aorta models has been extensively studied and reported here. The effects of pressure and arterial anatomy on the flow dynamic were investigated. The distribution of complex flow and WSS is correlated with the localization of atherosclerosis. With the available results we can conclude that the thoracic aorta, with complex anatomy is the most vulnerable artery for the localization and development of atherosclerosis. The flow dynamics and arterial anatomy play a role in the localization of atherosclerosis. The patient specific image based models can be used to diagnose the locations in the aorta vulnerable to the development of arterial diseases such as atherosclerosis.

Dynamic Hedging with Credit Default Swaps: Empirical Evidence from the European Monetary Union

This thesis investigates the effectiveness of time-varying hedging during the financial crisis of 2007 and the European Debt Crisis of 2010. In addition, the seven test economies are part of the European Monetary Union and these countries are in different economical states. Time-varying hedge ratio was constructed using conditional variances and correlations, which were created by using multivariate GARCH models. Here we have used three different underlying portfolios: national equity markets, government bond markets and the combination of these two. These underlying portfolios were hedged by using credit default swaps. Empirical part includes the in-sample and out-of-sample analysis, which are constructed by using constant and dynamic models. Moreover, almost in every case dynamic models outperform the constant ones in the determination of the hedge ratio. We could not find any statistically significant evidence to support the use of asymmetric dynamic conditional correlation model. In addition, our findings are in line with prior literature and support the use of time-varying hedge ratio. Finally, we found that in some cases credit default swaps are not suitable instruments for hedging and they act more as a speculative instrument.

Pectus excavatum: abordagem terapêutica

The pectus excavatum treatment has two different approaches: non-surgical techniques (modified dynamic thoracic compressor, exercises and the vacuum bell) or surgical techniques (silastic or solid silicone implant, open surgical repair like sternochondroplasty and minimally invasive repair). The introduction of Nuss procedure improved the pectus excavatum treatment, but its low acceptance was due to the high complication rate (e.g. cardiac perfuration). The thoracoscopy use for bar mediastinal passage reduced the complication rate. In comparison with sternochondroplasty, the Nuss procedure has smaller incision, less blood loss and less operative time. However, it has more reoperations, complications, longer hospital stay and more readmission rates, more time of thoracic epidural catheter for postoperative analgesia and more need for analgesic after being discharged. Although Nuss procedure has been used in children, patients under ten years must be only observed. The Nuss procedure is applicable to moderate or light symmetrical pectus excavatum, without costal protrusion, in young and adolescents patients. Furthermore, the sternochondroplasty is applicable to severe or asymmetric pectus excavatum, with or without inferior costal protrusion. Therefore, Nuss procedure and sternocondroplasty are not antagonistic procedures, and they must be used in accordance with a treatment organogram and the technique choice must be by functional and aesthetic outcome.

Development of racemization catalysts for dynamic kinetic resolution

Preparation of optically active compounds is of high importance in modern medicinal chemistry. Despite recent advances in the field of asymmetric synthesis, resolution of racemates still remains the most utilized way for preparation of single enantiomers in industrial scale due to its cost-efficiency and simplicity. Enzymatic kinetic resolution (KR) of racemates is a classical method for separation of enantiomers. One of its drawbacks is the limitation of target enantiomer yield to 50%. Dynamic Kinetic Resolution (DKR) allows to reach yields up to 100% by in situ racemization of the less reactive enantiomer. In the first part of this thesis, a number of half-sandwich ruthenium complexes were prepared and evaluated as catalysts for racemization of optically active secondary alcohols. A leading catalyst, Bn5CpRu(CO)2Cl, was identified. The catalyst discovered was extensively characterized by its application for DKR of a broad range of secondary alcohols in a wide range of reaction loadings (1 mmol – 1 mol). Cost-efficient chromatography-free procedure for preparation of this catalyst was developed. Further, detailed kinetic and mechanistic studies of the racemization reactions were performed. Comparison of racemization rates in the presence of Bn5CpRu(CO)2Cl and Ph5CpRu(CO)2Cl catalysts reveals that the performance of the catalytic system can be adjusted by matching of the electronic properties of the catalysts and the substrates. Moreover, dependence of the rate-limiting step from the electronic properties of the reagents was observed. Important conclusions about reaction mechanism were made. Finally, an alternative approach to DKR of amines based on space separated vessels was addressed. This procedure allows the combination of thermolabile enzyme with racemization catalysts active only at high temperatures.

Pienahitsien staattisen kestävyyden mitoitus perinteisesti ja eri reunaehtoihin perustuvilla parannetuilla mitoitusmalleilla

Tässä tutkimuksessa oli tavoitteena tarkastella analyyttisen laskennan keinoin pienahitsin mitoittamista ja selvittää käytännön kokeissa havaittu a-mitasta poikkeavan vauriotason sijainti poikittain kuormitetuissa pienahitseissä. Perinteinen laskentamallin tarkastelu laa-jennettiin koskemaan mielivaltaisessa kulmassa olevaa laskentatasoa ja suurimman yhdistetyn jännityksen perusteella löydettiin kriittisin leikkaus tasakylkisessä hitsissä. Lisäksi tarkasteltiin voimatasapainon huomioon ottamista mitoituksessa ja luotiin kaksi eri mallia tämän pohjalta. Kolme teoreettisesti oikeampaa mitoitusmallia täydennettiin kattamaan myös erikylkiset hitsit ja todettiin, että kaikilla mitoitusmalleilla erikylkiset hitsit ovat tilavuudeltaan optimaalisempia verrattaessa samanlujuisiin tasakylkisiin hitseihin.