ORGANIC CHEMISTRY, 3

Author: CASTRO MÁRMOL JUAN MIGUEL.
Year: 2004.
University: JAÉN.
Place of defense: FACULTAD DE CIENCIAS EXPERIMENTALES.
Place of preparation: FACULTAD DE CIENCIAS EXPERIMENTALES.

Author: GONZALEZ SABIN JAVIER.
Year: 2005.
University: OVIEDO.
Place of defense: FACULTAD DE QUIMICA.
Place of preparation: FACULTAD DE QUIMICA.

Summary: The nitrogen compounds such as amine, 1,2-diaminas and 2-aminoalcoholes optically active presents interesting applications in various areas of chemistry. These compounds are the structural foundations of ligands more effective in asymmetric synthesis and are present in a wide variety of biologically active compounds. The central theme of this report is the resolution of this type of nitrogen compounds through reactions catalyzed by lipases. The work is divided into four chapters. Chapter 1. It has been shown that the lipase B of the fungus Candida antarctica (CAL-B) is an effective catalyst for the resolution of some pharmacologically active amines such as amphetamine, similar o-, m-and p-metoxianfetaminas, mexiletina and 1-fenilbutan- 2-amine. It has also been shown that enantioselectividad exhibited by the enzyme towards these substrates not only depends on the difference in size of the substituents that carries carbon chirality. The work included in this chapter is in the next publication: Tetrahedron: Asymmetry 2002, 13, 1315. J. González-Sabín, V. Gotor, F. Rebolledo, "CAL-B catalyzed resolution of some pharmacologically interesting -substituted isopropylamines." Chapter 2. This chapter takes place resolving several 2-fenilcicloalcanaminas through reactions aminólisis catalyzed by different lipases. The experimental results show a strong influence on the size of the cycle and the relative configuration of the chiral centers in the enantioselectividad and the speed of reaction. Furthermore, studies have been performed molecular modeling in order to explain the differences observed in the reactions of aminólisis catalysed CAL-B. Based on these studies, we proposed to the enzymatic reactions of aminólisis an alternative mechanism of the enzymatic reactions of transesterificación, which produces the direct attack of the amine group carbonyl of acil-enzima without the mediation of the catalytic histidine . Part of this work is published in: Tetrahedron: Asymmetry 2004, 15, 481. J. González-Sabín, V. Gotor, F. Rebolledo, "Kinetic resolution of (Â ±) -trans- and (Â ±) -cis-2-phenylcyclopentanamine by CAL-B catalyzed aminolysis of esters. The key role of the leaving group." Tetrahedron: Asymmetry 2005, in press. J. González-Sabín, V. Gotor, F. Rebolledo, "Enantioselective acylation of rac-2-phenylcycloalkanamines catalyzed by lipases. Chapter 3. It has been found that lipase from the bacterium Pseudomonas cepacia is an excellent catalyst for the acetylation enantioselectiva several trans-2- (dialquilamino) ciclohexanoles and trans-2- (dialquilamino) ciclopentanoles racémicos with vinyl acetate as a giver of acilo and ether tert - butil methyl as a solvent. Moreover, it has demonstrated the usefulness of these aminoalcoholes optically active as ligands in the addendum enantioselectiva of dietilzinc to benzaldehyde. This work is published in: Tetrahedron: Asymmetry 2004, 15, 1335. J. González-Sabín, V. Gotor, F. Rebolledo, "Chemoenzymatic preparation of optically active -aminocyclohexanols and their application in the enantioselective addition of diethylzinc to benzaldehyde. Chapter 4. It has developed a method quimioenzimático very effective for the synthesis with high yields and excesses enantioméricos (ee) of various diaminas N N-disustituidas arising from the trans-ciclohexano-1 ,2-diamina and trans-ciclopentano- 1.2-diamina. From these diaminas have synthesized various derivatives have been employed as ligands in the addendum enantioselectiva of dietilzinc to benzaldehyde. In addition, as one of the 1,2-diaminas optically active, it has developed a simple and efficient synthesis of isomer active 8 of anal 3de gésico U-50488. Part of this work has been published in: Chem. Eur. J. 2004, 10, 5788. J. González-Sabín, V. Gotor, F. Rebolledo, "Chemoenzymatic preparation of optically active trans-cyclohexane-1 ,2-diamine derivatives. An efficient synthesis of the analgesic U (-) -50, 488"

Author: FERNANDEZ SOLARES LAURA.
Year: 2005.
University: OVIEDO.
Place of defense: FACULTAD DE QUIMICA.
Place of preparation: FACULTAD DE QUIMICA.

Summary: In recent years, development of methods biocatalíticos has allowed the preparation of a wide variety of products with high added value through the process very simple, selective and inexpensive, which has made it possible for some of them have been able to perform on an industrial scale. In this report, structured into three chapters, has been carried out the synthesis and resolution of different compounds of biological interest and therapeutic via enzymatic hydrolysis reactions and acilación. Chapter 1. It describes a new and concise strategy for the synthesis of the drug (S )-(+)- Zopiclone that presents an easy applicability to industrial scale. This process included as a key step enzymatic hydrolysis of a number of new intermediate carbonates. We also have analyzed the parameters affecting the selectivity of these processes, such as biocatalizador, solvent, water concentration, pH and additives. The results are reflected in studies: L. F. Solares, M. Diaz, R. Brieva, V. M. Sanchez, M. Bayod, V. Gotor, "Enzymatic resolution of carbonate new intermediates for the synthesis of (S )-(+)- zopiclone," Tetrahedron: Asymmetry 2002, 13, 2577-2582. J. M. Palomo, C. Matthew G. Fernández-Lorente, L. F. Solares, M. Diaz, V. M. Sanchez, M. Bayod, V. Gotor, J. M. Guisán, R. Fernández-Lafuente, "Resolution of () -5-substituted-6- (5-chloropyridin-2-yl) -7-oxo-5 ,6-dihydropyrrolo [3.4 b] pyrazine derivatives-precursors of (S) - ( +) - zopiclone, catalyzed by immobilized Candida antarctica lipase B in aqueous media ", Tetrahedron: Asymmetry 2003, 14, 429-438. M. Bayod, V. M. Sanchez V. Gotor, R. Brieva, L. F. Solares, M. Diaz, J. M. Guisán, J. M. Palomo, R. Fernández-Lafuente, "New carbonates as optically active intermediates in the synthesis of (+) -zopiclona" IS Patent 2203319. Chapter 2. It has developed a synthesis quimioenzimática for the synthesis of antidepressant (S )-(+)- citalopram (escitalopram), which greatly improves performance over other previous methods. The enzymatic step consists of a acilación or hydrolysis in the presence of lipases, and highlights mainly because the enzyme recognizes a functional group which is four links away from the center estereogénico quaternary present in the molecule. This work has resulted in the following publication: L. F. Solares, R. Brieva, M. Quiros, I. Llorente, M. Bayod, V. Gotor, "Enzymatic resolution of a quaternary stereogenic center as key step in the synthesis of (S )-(+)- citalopram," Tetrahedron: Asymmetry 2004, 15, 341-345. Chapter 3. It has studied the synthesis and resolution piperidinas 3,4-disustituidas trans and cis interest through biological processes or acilación enzymatic hydrolysis. Lastly, have tried to rationalize the results obtained through the Molecular Modeling.

Author: VENTURA MASIP RUBEN.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: UNIVERSIDAD DE BARCELONA, FACULTAD DE QUÍMICA.

Summary: The main aim of the thesis focuses on the synthesis of a family of polymers based on polyethylene, which has joined bioactive molecules at their ends, for application in the medical field. These polymers because they have two points are called bioactive ligands diméricos. Polymers trade are typically polidispersos thus has developed a methodology that has allowed sínteis polymer in solid phase in a controlled manner and thus polymers defined size. It opted for polyethylene polymer type, and specifically poliamida-polietilenglicol due to its good biocompatibility. Specifically joined withthe related molecules of adenosine receptors and dopamine, which receptors are involved in Parkinson's disease. In addition, it is known that these receptors can be as Parkinson's. It has developed a methodology for a synthetic adenosine antagonist of high affinity to the recipient, XAC, one of dopamine receptor agonist, PPHT. Once seha available sufficient quantities of these products have been explored to poderias modify their structures and enter into the ligands diméricos, ie derivatizarlas with polímros. For this study, we have synthesized two quimiotecas compounds, 23 and 16 compounds respectively, and biochemical tests have relieved two molecules that allow us to synthesize ligands diméricos without these biomolecules lose affinity with their respective receptors. Once the strategy was available synthetic polymers in solid phase, and how to unite biomolecules this polymer, we moved on to the synthesis of the ligands diméricos, synthesizing compounds until 7 carvings polymeric different. It is also synthesized monomers of the ligands, in order to study the effect of our polymer molecules. The difference between dímero and monomers is that the dímero is two bioactive molecules, one on each side of the polymer, while the monomer was available only bioactiva a molecule at one end. They are synthesized 8 homodímeros of XAC, 8 homodímeros of PPHT, 8 monomers PPHT and 8 heterodímeros of PPHT-XAC. The results of biochemical tests can be concluded that the dimers reveal cooperatividad oligomers in the receiver, being the first test of that described both in the case of homodímeros of XAC as in the case, more interestingly, the heterodímeros of XAC-PPHT.

Author: NIETO SUAREZ MARINA.
Year: 2005.
University: VIGO.
Place of defense: FACULTAD DE CIENCIAS DE OURENSE.
Place of preparation: FACULTAD DE CIENCIAS VIGO.

Summary: This includes a Ph.D. thesis research work which is intended to help in the search for and development of new pharmaceutical formulations that allow insulin oral administration, ensuring adequate levels of the hormone in the blood. Here, we studied the effect that can play different cilodextrinas (beta-ciclodextrina and y-ciclodextrina) in stabilizing the protein and improving its biodosponibilidad. The report contains a number of studies on the influence they can exert macrociclos both on the structure d ela insulin on the permeability of different models of this membrane protein. It uses the technique demonocapas surface Langmuir and yielding easily model membrane, and also has the advantage of allowing people to study as various parameters affecting the properties of these systems. Thus, in the same building were employed phosphatidylcholine and esfingomielina because these phospholipids major components of biological membranes. The results show that ciclosextrinas, dissolved in the subfase, affect the behavior of pure topcoat of phospholipids, altering the molecular order within these thin films. Furthermore, the magnitude and direction of this alteration depend on the pH and the presence of ions in the subfase. The topcoat insulin, cyclodextrins stabilize the tertiary structure of the monomers only when the pH of the subfase is close to the point isoeléctrioc peptide. Also, do not cause the dissociation of oligomers formed in the presence of cations Zn2 +. The changes caused by macrociclos in the properties of topcoat mixed esfingomielin / insulin extended at the interface arise mainly from the interaction of these molecules with the phospholipid.

Author: PRADO GONZÁLEZ ANA DE.
Year: 2005.
University: OVIEDO.
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: This report is divided into three sections according to the three main topics on which it has studied the involvement of the complex carbenos Fischer: synthesis of polymeric media, synthesis esteroselectividad and formation and reactivity of carbenos Fisher not stabilized. The first chapter describes the first synthesis directly on a polymer support, complex carbeno Fischer. In addition, it has revealed the involvement of systems polímero-carbeno obtained, in a reaction and cilopropanación, with the possible regeneration of the system to involve it in a second round of synthesis. The second chapter contains a summary of three new alcoxicarbenos Fisher enantioméricamente cigars and their participation in reactions synthesis diastereoselectiva. Thus describes the processes Diels-Alder, Mukaiyama-Michael or carbociclaciones [2 +1] leading to compounds enantioméricamente pure derivatives norborneno,? -butenolidas And ciclopropanos highly funcionalizados respectively. Finally, the last chapter describes the synthesis, characterization espectroscópica and reactivity preliminary first alquenilcarbeno Fischer not stabilized by heteroátomo a transition metal group 6. Studies conducted for the final achievement of the synthesis of carbeno not stabilized has revealed the existence of highly reactive intermediates with different patterns of reactivity depending on the conditions of the process which can be used for access to new structures.

Author: PEREZ FERNANDEZ DANIEL IGNACIO.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: CENTRO SUPERIOR DE INVESTIGACIONES CIENTIFICAS. INSTITUTO DE QUIMICA MEDICA..

Summary: The two main histopathological lesions of Alzheimer's disease are the senile plaques and neurofibrillary tangles. The main component of the neurofibrillary tangles is the protein tau hiperfosforilada. This phosphorylation of the protein kinase is regulated primarily by glycogen synthase kinase 3-beta (GSK-3beta) A good therapeutic strategy to reduce the phosphorylation of GSK-3beta and avoid the formation of neurofibrillary tangles would be through the use of inhibitors this protein. Starting from a seed collected from our quimioteca compounds that inhibia this protein, several changes were made synthetic in order to obtain more potent compounds. Once synthesized were carried out various studies both theoretical and experimental. First compounds not competing with ATP for the active site of the enzyme, the main advantage over the rest of inhibitors described in the literature. A study ComFA in order to obtain a model capable of predicting the biological activity of new structures. The derivatives were synthesized can pass through the membrane biological after testing cell in which noted the decrease in phosphorylation of the protein tau. The halometilcetonas were targeted in a variety of protein kinases present in the system nevioso Central and the union was measured at different neural receptors involved in Alzheimer's disease. Through theoretical and experimental studies found that the compounds were able to pass the blood-brain barrier and provide a good oral absorption. By HPLC was measured their degree of binding to plasma proteins other than noting that the compounds not joined them thereby encontarían in a high proportion in the body. Finally one of the derivatives of thiophene, also showed a dual action on the one hand inhibited the enzyme GSK-3beta and another showed anti-inflammatory activity.

Author: GARCIA DELGADO ANA BELEN.
Year: 2005.
University: OVIEDO.
Place of defense: FACULTAD DE QUIMICA.
Place of preparation: FACULTAD DE QUIMICA.

Summary: This memory comes from a collaborative project (Universidad-Ficyt-Empresa) between the chemical company Astur Pharma S. A. And the Department of Inorganic and Organic Chemistry at the University of Oviedo. The project aimed at the synthesis and study of the biological activity of new structural analogues of rifabutin against the bacillus causes tuberculosis. The results are described in the memory into two distinct chapters. Chapter 1 contains the synthesis of new 4-piperidonas products extensively studied in our research group. It describes two different methodologies for their preparation. - diaril-4-piperidonas. The second method allows the use of the (S) -prolina as a catalyst, the training of 2-amino-1 ,3-butadienos spot after reacting with imina lead to cicloaductos quickly, easily and scale multigramo. Chapter 2 is divided into two parts. In part A, describes the synthesis and structural elucidation of the analogs of rifabutin obtained by the reaction between the 4-piperidonas synthesized in chapter 1 and the precursor 3-amino-4-imino-rifamicina S. In part B, detailed studies of biological activity in vitro conducted with the new derivatives versus strains of Mycobacterium tuberculosis; these tests show high potential antimicobacteriano of our compounds. Also, data are collected obtained by theoretical calculations of molecular dynamics of the complex fármaco-enzima supporting experimental results found.

Author: CONCELLON FERNANDEZ CARMEN.
Year: 2005.
University: OVIEDO.
Place of defense: DEPTO DE QUIMICA ORGANICA E INORG.
Place of preparation: FACULTAD DE QUIMICA.

Summary: This report describes new applications in organic synthesis, diyoduro samarium, with the aim to develop simpler and selective changes that previously described, or develop new synthetic applications of diyoduro samarium. The first chapter gives results in the reduction reaction acids, esters or amides, -acetilénicos promoted by diyoduro samarium, in the presence of water deuterada. This new methodology is fast and generally allowing obtain easily, esters, amides and acid 2,2,3,3-tetradeuterados both aliphatic and aromatic, with high yields. It should be noted that water deuterada is the agent deuteración cheaper and easier to acquire, to mark organic compounds with isotope deuterium. If instead of using water deuterada is used H2O yields the corresponding esters and carboxylic acids amides saturated. The second chapter describes the synthesis estereoespecífica of (2R * 3S *) and (2R *, 3R *) -2-hidroxi-3-yodoamidas from transmission and cis-epoxiamidas using diyoduro samarium. This methodology is generally as they are available yodohidrinas aliphatic (linear and cyclic), unsaturated and aromatic. This transformation is one of the few examples in the literature, in which the SmI2 serving as a source of iodides, instead of as a reductant. The third chapter discusses two methods to help set up reactions training links CC, both promoted by diyoduro samarium. First, it describes the synthesis of different nitrated derivatives, as of aldehydes and ketones. The reaction of Henry, carried out with bromonitrometano and diyoduro samarium, is the first example described a reaction nitroaldólica promoted by SmI2. Likewise, neither the sodium iodide had been used previously to obtain 1-bromo-1-nitroalcan-2-oles, by reaction of aldehydes with bromonitrometano. In the second part of this chapter, has described a new methodology for obtaining 3-hidroxiácidos (precursor compounds and major subunits of natural products), from aldehydes and ketones, acid yodoacético, in the presence of SmI2. The most remarkable aspect of this reaction is the formation of a liaison CC, in the presence of an acid group. A mechanism has been proposed to explain this transformation in the fourth and final chapter, reflects two methodologies to help set up sequential reactions, adición-eliminación, promoted by diyoduro samarium. First, it describes the synthesis of esters, -insaturados, from aldehydes and dibromoacetato Ethyl, in the presence of SmI2. When performing the same reaction with ketones, are obtained 2-bromo-3-hidroxiésteres, which are difficult to prepare for their high tendency to epoxidar using other methods previously described. In the second part of this chapter develops a method for obtaining acids, -insaturados, by reaction of acid dibromoacético with different aldehydes. Again, the most remarkable aspect is the use of SmI2 to carry out the formation of a liaison CC, in the presence of an acid group.

Author: Chávez Uribe María Isabel.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: Facultad de Ciencias (Edificio Biológicas).
Place of preparation: CENTRO DE INVESTIGACIONES BIOLOGICAS.

Summary: The research work that is the thesis, are studies to understand the origin of the especificiad and stability of energy and structural forces that are involved in the process of molecular recognition carbohydrate protein, using domains heveína as models interaction, including in-depth analysis of the contribution of the role played by interaction aplamiento CH-pi, van der Waals and hydrogen bond on the interaction proteína- carbohydrate. In addition to continuing with the study of plant lectin and its interaction with carbohydrates. Studies were carried out by applying Nuclear Magnetic Resonance. The first chapter is the study of determining the structure 3D of a peptide mutant AcAMP2Pff18/Pff20 and their interaction with triacetilquitotriosa, the second chapter is the study of association of mutant Hev32S19D with peptide N, N ', N''N' ,''N''''-pentacetilquitopentaosa and dervidado monodesacetilado at the end reducer, finally the third chapter is the study of structural determination 3D of a peptide isolated from the tomato and its study with oligomers of chitin. The methodology that was used to conduct this research were NMR experiments, progamas DYANA and CYANA applied for the calculation of determining the structure 3D and the application of molecular dynamics calculations.

Author: NOUREDDINE BELMADOUI.
Year: 2005.
University: POLITÉCNICA DE VALENCIA.
Place of defense: UNIVERSIDAD POLITÉCNICA DE VALENCIA.
Place of preparation: UNIVERSIDAD POLITÉCNICA DE VALENCIA.

Summary: The knowledge of the photochemical reactivity and reaction mechanism of the drugs is essential to anticipate and prevent potential adverse effects caused by certain drugs for patients when administered orally or topically. In particular, the reactions of biomolecules fotosensibilizadas Drug key processes are at the origin of these side effects. Since including fotocarcinogenicidad is undoubtedly the most worrisome is important mechanistic study of the modifications photochemical DNA and its components are sensitive to drugs. Also, it is of great interest to investigate the possible estereoselectividad of the processes involved, for the convenience of using one of the two enantiomers in the case of chiral drugs. In connection with the possible enantioselectividad of drugs fotosensibilizan damage to DNA have produced two bicromóforos diastereomers by union chirality of naproxen (RoS) to the position 5 'sugar thymidine. It has found an important chiral discrimination involving the excited state of naphthalene in the following processes: A-deactivation physics in the presence of singlet molecules capable of forming hydrogen bridges. B - The transfer of energy singlete-singlete from thymine to naphthalene. C-deactivation in the excited state hat trick of naphthalene. Another part of this work has focused on trying to establish the dominant mechanism in the fotosensibilización of thymidine free drugs by having the cromóforo benzophenone. We have submitted studies fotólisis flash laser S-ketoprofeno (enantioméricamente pure) as acid fenofíbrico (AF) and its metabolite fenofibrate (FB) in the absence and presence of thymidine. But in the DNA contribution of the transfer of power might be higher, due to the lower energy state of thymine hat trick in the biomacromolécula. To better understand this process (training oxetanos) have prepared two díadas joining covalentemente thymidine in a derivative of benzophenone, S-ketoprofeno at positions 5 'and 3' sugar. It has been found that the spatial orientation of benzophenone and thymine in díadas studied has a great influence on the fotosensibilización intramolecular of thymidine by ketoprofen, and that the predominant mechanism that is also a cicloadición of Paterno-BÃ ¼ chi lead to a mix four oxetanos regions and stereoisomers. The ability of BP for the abstraction of hydrogen from the methyl group thymine has also been confirmed. Thus, birradical intermediate formed during this process could ciclar after docking intramolecular, forming a link CC. Furthermore, experimental evidence has been obtained that have shown that oxetanos macrocíclicos obtained suffer photochemical process of ciclorreversión adiabatic after irradiation directly, leading to the departure of díada in its excited state hat trick. This photochemical process, unusual, it is more efficient than the reaction of retro Paterno-BÃ ¼ chi of oxetanos obtained by fotocicloadición intermolecular between derivatives of thymine and benzophenone.

Author: VIDA POL YOLANDA.
Year: 2005.
University: MÁLAGA.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS - UNIVERSIDAD DE MÁLAGA.

Summary: It has conducted the synthesis of new types ciclofano macrocyclic structures containing complexing groups fotoactivos. The use of high dilution conditions in the final step of condensation intramolecular, in the synthesis of these compounds has been successful in the case of systems type all-heterahomocalixarenos. The structure of coronafanos where the group fotoactivo this is a aril-bencil-éter influences fotofísicas properties of the same, with one case interactions between aromatic rings of macrocycle both in the ground state and in the excited state. The photochemical reactivity shown by these compounds involves reactions transposition foto-Claisen. The presence of metallic cations influences both properties fotofísicas these ciclofanos as in the regioselectividad of the photochemical reaction. In those ciclofanos containing a unit of benzophenone in its structure, this is the dominant properties fotofísicas of them. They took place a very effective energy transfer from the unit metoxitolueno towards unity of venzofenona not fluorescence emission was observed in these cases. The photochemical reactivity shown these ciclofanos is through reactions intramoleculares capture hydrogen excited by the state group carobnilo the unity of benzophenone, generating a birradical positions 1.5. It moves towards the formation of a cycle of five members and leads to the corresponding benzofuranos arising after subsequent dehydration. The structure of the macrocycle is lowered tensions generated by the rotations necessary for the docking of you radicals take place hinder this process and the reaction goes in the other direction, giving rise to products transposition. The presence of metallic cations influences both the process of capturing hydrogen as the link radicals for training cycle.

Author: ALONSO XALMA MÓNICA.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA-PAR CIENTÍFIC DE BARCELONA.

Summary: The alfa-aminoácidos are organic compounds that have been the subject of numerous studies on its synthesis. Unquestionably their biological significance both for his role in the formation of proteins and peptides, by the enormous number of biological activities and played as a constituent of drugs. From here comes the need to find new synthetic routes that allow us to access these amino acids can be easily and effectively. As objective of this dissertation is the synthesis of new amino acids conformacionalmente restricted (acid derivatives 1,2,3,4-tetrahidro-isoquinolin-3-carboxílico, Tic), different N-Fmoc-aril-alaninas and mesitilglicina enantioméricamente pure and beta-hidroxi-alfa-aminoácidos aliphatic and aromatic, with a special interest in acid (2R, 3R) -2-amino-3-hidroxi-3-ciclohexil-propanoico, a key component in the synthesis of the drug anti-inflamamtorio and anti-HIV ONO-4128. It has been synthesized N-Fmoc-mestilglicina and has proven its applicability in the synthesis of peptides incorporating a tripéptido. We have also prepared various alanine and beta-hidroxi-alfa-aminoácidos from dioles enantioméricamente cigars. It has developed the first asymmetric synthesis of amonoácidos derived from Tic through reaction epoxidación and "ring-closing-metathesis." Some of these amino acids were tested as inhibitors of beta-catenin (protein involved in the tumorgénesis colon), hallándose including at least one potential inhibitor of beta-catenin. Lastly, has been prepared at multigramo acid (2R, 3R) -2-amino-3-hidroxi-3-ciclohexil-propanoico through the formation of a cyclic sulfate in a single step, exploring this novel reaction to others substrates with good results.

Author: ALGUERÓ CAMA BERTA.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAT DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA DE LA UNIVERSITAT DE BARCELONA.

Summary: It has developed a new methodology that allows unite covalentemente the antisense oligonucleotide and its mRNA by forming interleavings units trans-Pt (NH3) 2. First, two derivatives were synthesized nucleoside fosforamidito with imidazole groups and tioéter join nuclebase respectively, which allow incorporate such changes in the methodology oligonucleotides following standard fosfito triéster. The introduction of these new functional groups in the extreme 5 'does not substantially affect the stability of the duplexes with complementary chain. We have conducted tests platinación of olignonucleótidos modified small to assess the ability of new functional groups to coordinate the metal ion, as well as oligonucleotide sequence mixed with one or two changes in the extreme 5 '. Based on the results obtained are designed for cross two strategies: through hybridization of adduct intracadena oligonucleotide modificado-transplatino to chain up, either on the antisense oligonucleotide duplexes / complementary chain and adding transplatino. In both cases it has obtained the same adduct intercadena. The characterization of all adducts platinados has been carried out by oxidation with H2O2 and enzymatic digestion and subsequent analysis by espectormetría mass Maldi-Tof. In experiments has concluded that the best combination involves the introduction of nucleoside with the group Imidazol in the extreme 5 'antisense oligonucleotide, followed by nucleoside with the group tioéter. In the reaction with trasnsplatino is formed quickly and regioselectivamente an adduct intracadena in which the platinum coordinates a nitrogen imidazólico and sulfur tioéter. The reaction of intersecting takes place so that the metal ion of sulfur migrates to nitrogen 7 of guanine nucleotide opposite the changed with the group tioéter, manteniéndose unchanged union nitrogen imidazólico the chain antisense. The presence of a unit trans-Pt (NH3) 2 entrecruzando both chains comprises a large increase in the thermal stability of the duplex. Finally it has been shown that the reaction of intersecting only takes place when there is recognition between the chain and modified oligonucleotide complementary result of relevance to a possible application of eta methodology in the field of antisense therapy.

Author: CRUZ RICONDO LUIS JAVIER.
Year: 2005.
University: BARCELONA.
Place of defense: SALA DE GRAUS EDUARD FONTSSERÉ DE LA UNIVERSIDAD DE BARCELONA.
Place of preparation: UNIVERSIDAD DE BARCELONA.

Summary: The memory of this thesis is structured around two main themes: The first part is devoted to the application of synthetic peptides in the field of vaccines, and specifically the immunological characterization and evaluation of different strategies for tabling synthetic peptides the gp120 from HIV-1. The second part focuses on complex structures with marine-derived anti-tumor potential applications, particularly in the synthesis, structural determination and assessment of the antitumor activity of IB-01212 and its analogs.

Author: VILARÓ COSTA MARIA.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAT DE QUÍMICA.
Place of preparation: FACULTAT DE QUÍMICA (UNIVERSITAT DE BARCELONA).

Summary: This thesis is divided into two parts: Part 1-SUMMARY OF PARALLEL IN A LIBRARY ANÁLOGOS OF DIFLUNISAL: transtiretina (TTR) is one of the twenty proteins that are related to any of the amyloid diseases, including the Alzheimer's it is the best known. The TTR is a carrier protein, plasma, the thyroid hormone thyroxine (T4), the molecule that contains four yodos in its structure. The evidence of what the tetrameric form of the protein is more stable when it is coupled with the T4 has opened a new strategy for drug development. Among the most nominated compounds as inhibitors of related TTR amyloidosis, is the drug diflunisal, is the most active derivative iodized. This paper presents the parallel synthesis of a library of analog diflunisal with variations in the ring 2,4-difluorofenílico. First, it has developed a synthetic method for preparation of the structure bifenílica of analogues diflunisal through a coupling reaction crossfire between Suzuki acid 5-yodosalicílico and a series of acid arilborónicos commercial conditions using reaction soft (i aqueous medium temperature). Using these conditions, and by a team of parallel synthesis (Advanced Chemtech, 440 SOM), has prepared an initial library analogues diflunisal. The next stage of reaction, which gets a second library consists of a iodization electrofílica aromatic using for the first time a version supported reagent iodization Barluenga (IPy2BF4). The biological activity of different compounds of libraries has been tested by a method turbidimétrico screening high efficiency (HTS; high throughput screening), developed in the Laboratory of Biochemistry, IQS. PART 2 .- MODIFICATION POST-SINTÉTICA OF PÉPTIDOS One of the most interesting applications of the methods of modification post-sintética is the possibility of exploring other biological structure correlations greater diversity than is conferred with the códifo of 20 amino acids natural. On the other hand, avoids the work of synthesis and processing pre-derived amino acid of interest and construction, step by step, new sequences from them. The main limitation of this approach is the lack of compatibility of the substances peptide with many of the traditional methods of organic chemistry. The experience in our laboratory reagent of iodación of Barluenga, IPy2BF4 for iodization electrofílica delas side chains of tyrosine and phenylalanine has led us to explore methods for preparing these yodopéptidos In particular, the reaction catalyzed coupling crossed Suzuki by Pd. Thus, in this paper, described one of the first examples of modifications post-sintéticas based on acomplamiento Suzuki, different substrates peptídicos, derived from endefalinas, containing residues of 3,5-diyodotirosina i 4-yodofenilalanina with different acids ariborónicos. The condidiciones reaction has been restricted to use exclusively, medium and accuse room temperature.

Author: URBANEJA BIOSCA XAVIER.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAT DE FARMÀCIA.
Place of preparation: FACULTAT DE FARMÁCIA.

Summary: The reaction coupling enolatos ketone and vinyl halides catalysed by Pd (0) was described by Piers in 1990. Despite being a very appropriate methodology for the preparation of polycyclic systems has been ignored for a long time, and the few examples that exist only describe alfa-alquenilación ketones. In this Doctoral Thesis, and as a continuation of the work carried out within the research group on the coupling intramolecular of enolatos ketone and vinyl halides or arilo catalysed Pd (0) in nitrogen systems, the reaction has been studied over another nucleófilo type enolato such as nitronatos beta y-insaturados. The completion of this study methodology has been found that the process is extremely complex claimed. However, it has been able to perform satisfactorily coupling intramolecular of nitronatos beta y-insaturados both vinyl halides as arilo, as they have been found conditions reaction, and using PhOK as a base, well suited to such processes. For this reason, it was decided to explore the use of PhOK based on links intramoleculares of enolatos ketone and vinyl halides, and was later extended to other systems such as esters and nitrilos, precursors of anionic species stabilized. The results obtained by using this database has been very successful, since it prevents the process side compete with the coupling, and the amount of catalyst can be reduced. Moreover, this reaction is very reproducible and without the need to take special precautions (can be done even in the presence of water). The fenóxido could have additional functionality to the base, as seen in a working Buchwald, which uses the PhOH as an additive in reactions arilación ketones. Thus, in line with what the proposed believe in the existence of an intermediate stable paladio-fenóxido that facilitates enolización of compounds through coordination of the carbonyl group of the substrate of departure. The existing work on the alquenilación of enolatos ketone suggest that the reaction conditions developed in this Doctoral Thesis are more general described so far. In a second part of this report, applies the methodology alquenilación ketones catalysed by Pd (or) successfully in the preparation of advanced intermediates in the synthesis of alkaloids natural estricnopivotina and calicifilina A.

Author: FARRERA SINFREU JOSEP MARIA.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: PARC CIENTÍFIC DE BARCELONA.

Summary: In recent years, the solid phase synthesis has become an essential tool for the synthesis of peptides and oligonucleotides. Although these areas have developed many complex in solid phase synthesis, it is still difficult to think of any molécular organic synthesis using this methodology. One of the most important issues presented in solid phase synthesis is the development of new strategies for synthesizing molecules can be obtained with a significant structural complexity in a quick and efficient manner. To achieve this, it may need branched central platforms. In this sense, and specifically in the synthesis of peptides and peptidomiméticos, amino trifuncionales play a key role. This thesis has been used amino acids trifuncionales to synthesize complex structures such as cyclic peptides or foldámeros and in the synthesis of quimiotecas. Mainly we worked with peptidomiméticos based derivatives trifuncionales proline, such as cis-gamma-amino-L-prolina and trans-4-hidroxi-L-prolina. These platforms have three functional groups that decorate the ring of five members with a provision suitable to be used as hearts of branched molecules. The first project where he worked was in the study group protectors orthogonal to the synthesis of tetra-beta-péptidos cyclical in solid phase using the spacer bifuncional BAL (1). In the course of these studies, in some cases were detected problems of incompatibility of the groups protectors Fmoc and Alloc, problems that could be remedied with synthetic methodologies appropriate (2). The second project in which we work was based on foldámerops derived from cis-gamma-amino-L-prolina. In the first part of this work, we describe the solid phase synthesis of these compounds, as well as its conformational preferences through studies of circular dichroism and magnetic resonance imaging (3). In the second part, I seek potential applications as carriers of drugs, considering its entry into eukaryotic cells through techniques fluorimetría plate, flow cytometry and confocal microscopy (3). In the third part of the thesis work on the synthesis of a quimioteca compounds potential inhibitors of lisil-tRNA synthetase (LysRS) of Plasmodium falciparum parasite causing malaria. It also developed a solid phase synthesis of sulfamatos.

Author: SÁNCHEZ SALGUERO LAURA.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: It has developed a general procedure to get pantolactamas differently substituted on the nitrogen by reaction of pantolactona and primary amines with acid catalysis in a reactor under pressure. The best result is obtained for N-fenilpantolactama and therefore is the one that is most suitable for studying its applications as chiral auxiliary in reactions deracemización of carboxylic acids alpha, alpha disustituidos to get in shape enantiopura the two enantiomers of derivatives Gaba and the drug Levetiracetam. It has also been used as an agent for the preparation of resolution in the form enantiopura of the two enantiomers of the drug baclofen and a series of N, O-Psiconucleósidos never described so far.

Author: PICÓ RAMOS ANNA.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA - UNIVERSITAT DE BARCELONA.

Summary: It has developed a new procedure for the preparation of gamma-amino vinyl sulfones from the corresponding 2 - (1-aminoalquil) oxiranos three-stage synthesis. Considering that the 2 - (1-aminoalquil) oxiranos of departure can be obtained from a wide variety of alcohols alílicos in any form estereoisoméricas, the method developed is highly versatile and estereoselectivo. There have also been prepared gamma-amino vinyl sulfones N-propargiladas, which have been used to obtain 3-azabiciclo [3.3.0] octenonas by ciclación of Pauson-Khand intramolecular. The result estereoquímico of ciclación has not only proved to be controlled by the structure of the substrate, but also by the metal complex carbonílico used. It has tried to exploit the versatility of 2 - (1-aminoalquil) oxiranos for preparing gamma-amino vinyl phosphonates, 4-amino-1-alquen-3-oles and oxiranil pirrolidinas. It has managed to carry out the first stereoselective synthesis of 2 - (oxiranil) pirrolidinas previously obtained in the form of mixtures diastereoméricas from (S) -prolinol. Finally, it also has prepared a library of 20 peptidil aril vinyl sulfones to allow future studies of structure in inhibiting a variety of cysteine proteases.