CARBOHYDRATES CHEMISTRY

Author: Ariza Aranda Jesús.
Year: 1993.
University: AUTÓNOMA DE BARCELONA.
Place of defense: Facultad de Ciencias..
Place of preparation: Departamento de Químicas. Facultad de Ciencias. Universidad Autónoma de Barcelona.

Summary: This report presents one hand and a first set of two sections, the way in which a natural as gamma-D-ribonolactona can be transformed into hidroxiaminoácidos not proteinogénicos, and on the other the potential applicability of these in training ring 2-azetidona of beta-lactámicos antibiotics. It describes the study of the Region and estereoselectividad at the opening of (2R, 3R, 4R) -3.4 -epoxi-4-metilbutirolactona with azide ion or acid hidrazoico in an attempt to corroborate the results obtained with other nucleotide about such openness also develop a methodology for obtaining alpha -aminolactonas. The formation of isomers in the reaction replacement nucleofílica by sodium azide on 2-O-tosil-5-desoxi-gamma-D-ribonolactona, 50, or at the opening by acid hidrazóico in (2R, 3R, 4R) -3, 4-epoxi-4-metilbutirolactona, 19, is a phenomenon inherent in the structure of the molecule. Otherwise, the epimerización C-2 ring butyrolactone is a phenomenon later á group substitution tosiloxi or the opening of oxirane ring. The substitution at position C-3 ring butyrolactone is crucial in the formation of a second isomer. It also described the synthesis of a new chiral precursor equivalent to the (2R, 3R, 4R) -3.4 -epoxi-4-metilbutirolactoha, 19, used in the synthesis of (-) -Blastmicinona, 54. overall it. Also describes the synthesis of a completely estereocontrolada of (-) -D-treo-gamma -hidroxinorvalina, 5, as well as (-) -D-eritro-gamma-hidroxinorvalina, 6, from gamma -D-ribónolactona, 11. The synthesis of 5 and 6 corroborates unique way of allocating the estereoquímica absolute done in other work on the structures of 5 and enantióraera, 6. Additionally, it describes the synthesis of a completely estereocontrolada and from gamma-D-ribonolactona, 11, (3S, 5R) -3-benciloxicarbonilamino-5-hidroximetil-2 (5H) -furanona, 77, pioneer in obtaining direct antibiotic Clavalanina, 2, isolated from the Streptomycea clavuligerus, which has been served a formal synthesis of this última.El procedure carried out in this work improved dramatically, in terms of operational and performance summaries published so far in the literature. The pilot study shows that when the 2-benciloxcarbonilamlno-2-desoxi-3 ,4-0-benciliden- 5 -D-ribonolactona, 90, was subjected to the action of a base, the product of contraction cancel (S) -3-benciloxicarbonilamino-5-hidroximetll-2 (5H) -furanona, 91. There is, moreover, that simultaneously obtaining 91 is the formation of benzaldehyde, it is suspected that prior to the phenomenon of contraction in itself is a movement of 6 electrons responsible for the formation of benzaldehyde. In an attempt to deepen the chemistry of these lactones, presents losdatos of a study on the applicability of the above process to different 3,4-O-benciliden- 5 -D-ribonolactonas heterosustituidas at C-2 and found that if though the removal of benzaldehyde takes place, the products of the same may follow different routes of degradation under the conditions of reaction or during the process of neutralizing them, according to the sensitivity of sustituyente located in C-2. On the other hand, describes a study on the implementation of 2-azido-2-desoxi- gamma -D-ribonolactona, 111, as a precursor in the synthesis of chiral (3R, 4R) -3-azido-4- ((S ) -2.2 - dimethyl-1 ,3-dioxalan-4-il)) -2-azetidona, 106, through derivatives amídicos. The results show that treatment with (-) -2-azido-2-desoxi-3-O-mesil-4 ,5-O-isopropiliden-D-arabinopentanamida, 115, which is based, does not give rise to the product ciclación expected but the product for disposal, and 8 s say 8cb to (S) - (trans) -2-azldo-4 ,5-0-isopropiliden-2-pentanamida, 114, and with quantitative yields. This fact and low returns in each of the synthetic steps prior to the attempted ciclación show that the gamma-lactonas can not be considered, at least through derivatives amídicos as optimal precursor for the creation of the ring 2 - azetidona in the synthesis of beta-lactámicos derivatives. The report describes the study on the possible applicability of 2-azido-2-desoxi-3 ,4-O-benciliden- Delta -D-ribonolactona, 56, as well as 2-benciloxicarbonilamino-2-desoxi-3, 4 - O-benciliden- delta-D-ribonolaetona, 90, as chiral precursor in the synthesis of 106 through the direct conversion of both esters lactónicos in their hidroxamatos of rent or acilo-. However, the reaction conditions for obtaining the latter leading to degradation products through processes mentioned above. Applying the synthetic strategy already mentioned for 2-azido-2-desoxi- gamma -D-ribonolactona, 111, as well as for 2-benciloxicarbonilamino-2-desoxi- gamma D-ribonolactona, 120, towards the synthesis of 106, it has been proved the invlabilidad in the same mainly because under condicionee reaction, gamma-laetonas starting saponifican quickly or give replacement products at C-2, the high concentration of functionality in these substrates makes them unsuitable for training ring 2-azetidonas in the synthesis of beta-lactámicos derivatives.

Author: GÓMEZ GARCÍA MARTA.
Year: 2004.
University: SEVILLA.
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: SUMMARY OF THE THESIS DOCTORAL cells present on its surface a series of oligosaccharides attached to so covalent lipids (glycolipids) or proteins (glycoprotein). The glucídica portion of these glycoconjugates, "glicocálix", is involved in a variety of processes of communication between the cell and the environment that surrounds it. The role of carbohydrates as carriers of biological information has triggered the synthesis and characterization derived from carbohydrates not only act as ligands specific cell receptors. But it also can act as carriers of drugs. The work done in this thesis is part of this overall strategy for the development of new carrier-specific medicines based on the ability of inclusion of cyclodextrins and capacity for the recognition of carbohydrates for specific lectin. The CDs are carbohydrates inmunogénicos not of natural origin and biocompatible. Its hydrophobic cavity may contain other organic molecules in size and solubilizarlas and stabilized in water. The type CD-glicoligando resulting conjugates (CDs third generation) can form complexes ternary CD-fármaco-receptor biological interactions with simultaneous type receptor-huésped in the cavity of the CD and carbohidrato-proteína in the cell membrane tissues. Specifically, three new types of cyclodextrins third generation: dendritic CDs, conjugates CDs diméricas and CDs hiperramificadas. New research led to the design of cellular markers glucídicos recognition as the development of new derivatives of cyclodextrins suitable for conjugation. The results can be summarized as follows: 1 .- The conjugates type ciclodextrina-glicodendrímero have been shown to have better properties as carriers of drugs that cyclodextrins monovalent or cyclodextrins polisustituídas. The possibility of vectorizar the Taxotero @ to the surface of macrophages using derivatives manosilados multivalent demonstrates this concept. Moreover, the study's recognition of inclusion complexes by specific lectin suggests a new mechanism applicable to molecular transport systems multivalent: clusterización transporter molecule by the host. Supramolecular species resulting in higher valence formal. 2 .- The methodology developed allows tailor the transport element "to measure" of the molecule to transport, while preserving the properties of recognition by specific receptors. The preparation of cyclodextrins diméricas designed to form complex 1:1 type sandwich with Taxotero with constant association of more than 1000000 M-1, demonstrates this concept. 3 .- The incorporation of glicodendrones on the positions of the primary cyclodextrin leads to nano structures that are models of glicocálix cell. The use of heptakis [6 - (2-aminoetil) -6-desoxi] ciclomaltoheptaosa as core allows the preparation of these derivatives hiperramlftCados. - Utitizando the reaction of action de-1-tioazucaresa double bonds and from nucleus of pentaerittriol triallado. It is possible to design glicodendrones heterogeneous. Their incorporation into the cyclodextrin per (C-6) cisteaminiliada leads to heteroglicoclústeres where it is possible to control the density and the relative proportion of different epítopos glucídicos. The study of the properties of appreciation for lectin of these compounds has revealed the existence of secondary interactions in recognition carbohidrato-proteína operating at high density and formally involve the modification of the specific receptor (effect heteroclúster). These resul 8 ing its 390 gieren the existence of new mechanisms, independent of the concentration of primary ligand. In biological processes regulated by interactions carbohidrato-proteína.

Author: FERNÁNDEZ GONZÁLEZ MARTA.
Year: 2004.
University: SANTIAGO DE COMPOSTELA.
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: This dissertation studies were conducted addiction radicals generated fotoquímicamente systems C = N. It has been addressed addiction either version intramolular as in the intermolecular. 1. In his version intramolecular have been synthesized advanced intermediate gives tetrodotoxina holding the ring ciclohexánico and center quaternary nitrogen from derivatives glucofuranósidos. The key step was a reaction tandem addiction and ciclación 6-sexo on ether ettoxima installed in a position C3 of derivatives. 2. In his version intermolucular include the development of a simple and efficient method for the asymmetric synthesis of alpha amino acids. The key step was the addition of radical 1,3-dioxolanilo to N. Acilhidrazonas arising from the (S) -3-amino-4-bencil-oxazolan-2-ona xeneradas spot from the corresponding alpha-aminoácido.

Author: GARCIA GARCIA PORRERO ANGELA.
Year: 2004.
University: AUTÓNOMA DE MADRID.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS.

Summary: The interest in our group in the synthesis of aminociclopentitoles both natural and synthetic analogs and their evaluation as inhibitors of enzymes glicosilhidrolasas led us to consider expanding the methodology developed to the synthesis of various structural reasons carbocíclicos and enantiomericamente pure properly funcionalizados, with the so use them as frames molecular gifted two points diversity for the preparation of quimiotecas inspired by the structure of these natural products. The overall strategy is based on synthesis of the carbociclacion reductive carbonyl / imine promoted by diyoduro of samarium of iminocetonas polihidroxiladas from hexosas. He also raised the synthesis and study of enzyme similar structural trehazolina, potent and specific inhibitor natural enzyme alpha alha-trehalasas, from a common precursor prepared from D-manosa.

Author: DÍAZ PÉREZ PAULA.
Year: 2004.
University: SEVILLA.
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: The glicosidasas are widespread in the organisms and play a biological role crucial. The high number of physiological and pathological processes in which the glicosidasas has promoted an intense investigation led to identify specific inhibitors of the same. Among the inhibitors glicosidasas most studied are glicomiméticos (analogues monoscáridos) that the atom of oxygen endocíclico has been replaced by a nitrogen atom, known as iminoazúcares or azaazucares. The fact that iminoazúcares be good inhibitors glicosidasas gives them a great therapeutic potential. Some representatives of the families of compounds used to treat certain forms of diabetes. In some cases they have also shown properties antiinfectivas front of bacteria and viruses, including the human immunodeficiency virus (HIV), as well as properties anticancerígenas. In this thesis we have explored new strategies for the design and synthesis of highly specific inhibitors include, as variables to modulate the specificity, the following factors: controlling the loading densities in the glicónica, ability to set configuration center anomérico, shaping the rest of hydroxylated centers and introduction of sustituyeres of varying polarity. The objectives synthetic have focused on the following structures: analogues castanospermina, resulting hybrids castanospermina and trehazolina, analogues swainsonina and structures that incorporate the functional group guandino. In all cases, this is glicomiméticos nitrogen pseudoamídico in the ring for those who have been on the verge novel synthesis strategies. With glicomiméticos synthesized have been carried out studies to assess their activity as inhibitors of various glicosidasas. The results obtained in testing enzimológicos have allowed us to verify the validity of the hypothesis of departure and identify highly effective inhibitors (Ki until range nanomolar) sensitive to anomería. Combining aspects synthetics and enzimológicos has enabled us to also plan further structural changes to access inhibitors even more potent and specific. The best results were obtained for the glicomimético with structure 3-octilimino-2-oxaindolizidina with a profile similar to that of hydroxylation of D-galactopiranosa, who introduced inhibition constants in the range nanomolar off the beta-glucosidasas almonds and Beef liver, as well as a selectivity anomérica total. This derivative is a good candidate for possible use in studies of targeted therapies for diseases related to lysosomal storage disorders in the glycoconjugates as gangliosidosis GM1, disease neurodengerativa deadly for the treatment which does not yet exist.

Author: LÓPEZ PRADOS JAVIER.
Year: 2004.
University: SEVILLA.
Place of defense: INSTITUTO DE INVESTIGACIONES QUÍMICAS CENTRO DE INVESTIGACIONES CIENTÍFICAS.
Place of preparation: INSTITUTO DE INVESTIGACIONES QUÍMICAS. CENTRO DE INV. CIENTÍFICAS ISLA DE LA CARTUJA.

Summary: This thesis comes in an agreement between the CSIC and the company Rodaris Pharmaceuticals. The basic purpose of this convention, consisted in the development of biological products for the potential treatment for the disease developed resistance to the action of insulin and the elucidation of a hypothetical new mechanism for the action of insulin, called the hypothesis second messengers. In the first part, describing the methodology used to design molecules IPG type A, its synthesis and testing activity insolinomimética to which they were subjected. The second section describes the route of synthesis of a molecule that GPI presents its structure basis, in order to use it in future studies developed in our group investigaicón and contained in two doctoral dissertations.

Author: VERA AYOSO YOLANDA.
Year: 2004.
University: SEVILLA.
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: The glicoaminoácidos (GAA) can be used as a prefabricated blocks of great versatility in combinatorial chemistry and can be considered dipéptido-isósteros conformacionalmente restricted. It is also known that fluoridation of bioactive molecules in addition to increasing its power frequently biological improves the permeability and lipid metabolic stability. The trifluoride dietilaminoazufre (DAST) has been used extensively for fluoridation decarbohidratos. Our research group has described various types of transpositions promoted by DAST. These reactions that occur with or without ring contraction are a simple method for the preparation of fluorides glicosilo C-3 branched and 2,5-anhidro-1-fluoro-1-O-metilhexitoles equivalent synthetic aldehído-azúcares ( " formil C-glicofuranósidos "). Based on the foregoing, we made it our goal the preparation of new regional and stereoselective carbohydrate modified conactividad enzyme potential and in turn be used as precursors peptidomiméticos. As we considered this strategy for the extension of the methodology, based on reactions transposition promoted by DAST, cited above applying it to: A - Methyl 1,2-trans-diecuatorial- and 1,2-cis-glicopiranósidos for get formil C-glicofuranósidos, including precursors C-glicoaminoácidos (C-GAAs) with skeleton tetrahydrofuran. B-3-C-Ciano-3-etoxicarbonilhexopiranósidos as a route beta-aminoácidos fluorinated 3-C-ramificados freely conformacional restricted derivatives D-glucosa. The systematic study of fluoridation done on various methyl 2-hidroxi-hexopiranósidos unbranched configurations D-gluco, D-altro, D-alo and D-xilo with DAST, has enabled us to establish new criteria on the course of the reaction of fluoridation . Thus, when the hydroxyl group at position 2 is available in equatorial gives a 2,5-anhidro-1-fluoro-1-O-metilhexitol, which is the synthetic equivalent of a "2,5-anhidro-aldohexosa" . When the group 2-OH is axial may occur replacement nucleófila by fluoride, the reaction of removal or migration -1.2 group neighbor. Thus we have prepared a series of 2,5-anhidro-1-fluoro-1-O-metilhexitoles, which contain a feature aldhídica latent. His hydrolysis creates corresponding formil C-glicofuranósidos, which constitute a new kind of molecular platforms ( "Molecular sacaffolds"), whose potential for diversification has been demonstrated through the synthesis of C-glicosilderivados multifuncionalizados in rates ab: A - C-disacáridos: in a program aimed at developing vaccines against cancer artificial, led by Professor P. Vogel was projected using some of the formil C-glicosidos obtained in the synthesis of new C-diosacáridos through condensation induced Et2All between those aldehído-azúcares and enolatos derivatives ulosas. We have used some of the aldehído-azúcares or its synthetic equivalent, and even though they varied the conditions of reaction, we could not obtain the product of condensation. B-C-glicosilaminas: In collaboration with the group of Professor P. Vogel has been conducted synthesis C-glicosilaminas variously N-sustituidas by reductive amination of formil C-glicósidos previously obtained. The reaction unprotected with MeONa / MeOH 1M originates corresponding derivatives desacetilados with good yields. C-C-glicosilnitronas: "formil C-gllicofuranósidos" obtained can be transformed into N-bencilnitronas, which in turn can be used in the synthesis of C-glicoconjugados more complex. The nitronas may be involved in reactions cicloadición [3 +2] alquenos to give rise to isoxazolidinas. D-derivatives C-glicoaminoácidos multifuncionalizados: The use of our "formil azido-C-glicofuranósidos" has allowed laid down 8 er one and 669 ficiente path GAAs multifuncionalizados type tetrahidrofuránico well as their use in the synthesis peptidomiméticos simple. Moreover, it has conducted the study conformacional of new peptides synthesized with the aim of establishing a secondary structure to which they can give rise. In order to obtain Glicoaminoésters C-3 Tangled has studied the reaction of a series of methyl and 1-feniltio-3-C-ciano-3-etoxicarbonil-beta-D-glucopiranósidos with DAST, which has given rise to various fluorinated monosaccharides Tangled in C-3. The methodology developed is an easy route for the synthesis of glico-beta-aminoácidos fluorinated branched, enantioméricamente cigars and freedom conformacional restricted share the carbon with a ring piranosa. We assessed the capacity as inhbidores of glicosidasas and HIV some of the compounds synthesized.

Author: SÁNCHEZ RUÍZ ANTONIO.
Year: 2005.
University: MÁLAGA.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: The work described in this thesis is the concrete implementation of epoxiamidas chiral obtained by the condensation of iluros sulfur stabilized by an amide with chiral aldehydes derived from carbohydrates. This methodology has been applied to the synthesis of epoxipéptidos E-64, E64c and CA-074, as well as similar amides, and bengamidas, bioactive compounds with a mode of action remains to be elucidated. In both cases, it has employed a iluro sulfur stabilized by an amide of indolina as key compound, because once the condensation, it is feasible corrode the epoxiamida of indolina to indol-amida appropriate, which may or transamidarse with hydrolysed softness. Thus, in the case of epoxipéptidos, condensation of that iluro sulfur with 2,3-O-isopropilidén-D-gliceraldehído rendered the expoxiamida of indolina chirality for an unparalleled excess diasteremérico in favor of isomer 2S, 3R. This exposiamida leads to obtain compounds derived from the family of E-64c through developing the tip of acetal and coupling with the derivative peptídico corresponding to subsequently oxidize the indolina presents au sindol derived by oxidizing radicalarios as DDQ order, then proceed with its hydrolysis mild acid to release the final. However, for the preparation of S-64, it was found that the presence of a group bis-Boc-guanidino caused decomposition of the molecule in the process of oxidation with DDQ, being necessary to start from the indolamida derived from isopropilidén - D-gliceraldehído, could arrive at the final product and several similar amides. Once the proximity to exposipéptidos, began with the preparation of bengamidas using the olefinación Julia amended to prepare the alqueno terminal from aldehyde derivative 2,3-O-isopropilidén-D-treitol monoprotegido by a silil - ether. However, this reaction proved to be inadequate to pay for a mixture 1:2 of alquenos E: Z. Thus, alqueno Terminal E had to be introduced at the end of the synthesis, using a metátesis of olefins in the precursor end. A key step in the synthesis was the opening regioselectiva a epoxialcohol with methanol, using a novel phase settled methodology that employs trialquilboratos as activators of oxirane, allowing the product to get to opening in position 2 exclusively. Once this objective is reached to end forerunner, which underwent a reaction metátesis of olefins to install alqueno E terminal. This reaction got carried out by treatment with the catalyst Grubbs second generation of pioneering end in a mixture of 3-metil-1-buteno in dichloromethane, thereby good yields and excellent estereoselectividades in the generation of double bond. Leveraging the approach conbinatorial of our approach summarizes various analogues were prepared by amending alqueno terminal, by opening the epoxialcohol Intermediate different nucleotide, and by amending the lactam present in the product, thereby allowing to reach a library of compounds with the that attempt to determine the influence delas structural changes in their activity.

Author: MARI SILVIA.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: FACULTAD DE BIOLÓGICAS.
Place of preparation: CENTRO DE INVESTIGACIONES BIOLÓGICAS DEL CSIC.

Summary: During recent years it has been shown that carbohydrates are widely circulated by the nature and played a large number of biological functions. Today it is clear that the main biological role of carbohydrates is to be specific points of molecular recognition for lectin, toxins, enzymes and antibodies. In fact the processes of molecular recognition carbohydrate / protein involved in the folding and maturation of the glycoprotein in the cell adhesion, in the control of cell growth and other cellular activities, such as embryogenesis. From a general perspective, it is obvious that for the molecular recognition process takes place, the three-dimensional structures of carbohydrate and receptor plays a major role. From a rational point of view, and considering carbohydrates (or its synthetic analogues: glicomiméticos) as potential drugs, it is clear that an understanding of its structure in a free state as a partner to the receiver is important. Knowledge of the three-dimensional structure of the carbohydrate in solution can only be obtained through techniques of Nuclear Magnetic Resonance (NMR). If favorable, the use of NMR can also allow the determination of protein structural complete free or complex proteína-carbohidrato. However, we know that this experimental technique imposes severe limits on the size of the system. This limit is around 100 waste for proteins without marking siotópico, 150 for those labeled with 15N and around 300 for a double (15N, 13C) marked. However, even in the chaos that the size of the system is too big to get a full structural elucidation, NMR can, if favorable, providing information on the conformation of the ligand recognition in the center of the protein, ie on the possible formation bioactiva. Thus, through measures to effect Overhauser nuclear transfer (TR-NOE), it is possible to determine the conformation of the receptor and ligand partner, for example, detect conformational changes that occur when moving from the way free to associate. In this report we have focused on the study of the interaction between synthetic analogues (glicomimético) from various natural ligands, such as ganglioside GM1, and their biological receptors such as bacterial enterotoxin CT; lectina of muerdago and various glycosidasas using a multidisciplinary approach of organic synthesis, molecular modeling, NMR and measures of affinity. Furthermore, very recently, we have shown that it is possible to make STD experiments using living cells, and therefore without the need to isolate the receiver. The work has been done in collaboration between the laboratories of Anna Bernarid in Milan and Jesus Jiménez-Barbero in Madrid, first in the framework of an integrated action Hispano-italiana (HI2000-178) and then, within a European project, RTN-2002-00173, Glycidic Scaffold, that the candidate Silvia Mari has been hired as an intern Predoctoral, Early Stage Researcher, in the laboratory in Madrid since November 2002.

Author: ALFONSO PÉREZ FRANCISCO.
Year: 2005.
University: SEVILLA.
Place of defense: INSTITUTO DE INVESTIGACIONES QUÍMICAS.
Place of preparation: INSTITUTO DE INVESTIGACIONES QUÍMICAS. ISLA DE LA CARTUJA.

Summary: One of the most important aspects to elucidate the mechanism of the second messenger of the structure one of the IPGs mediators. The fundamental problem lies in the limited amount of IPG aislable of substrates natural assets, as well as structural changes that may accompany the process of extraction of these structures. In this regard, the role of the synthesis is essential for accessing defined structures that can be subject to structural and biological studies. These studies could give light on the assumptions of the second messenger and provide active substances for the treatment of diseases such as type II diabetes. This dissertation is aimed on the development of synthetic effective strategies for the preparation of various types of compounds IPG and its subsequent biological study. First, it has undertaken the preparation of pseudodisacáridos derivatives D L-Chiro-Inositol Glicosilados in position 1, improving the synthesis of these structural reasons with the development of new synthetic strategies that provide aceptores with symmetry C2. With the detailed study of these reactions intend to analyze the effect of configuration and acceptor of the substituents on the reactivity and esterreoselectividad of reactions glycosylation. Secondly, we have prepared pseudodisacáridos presenting the greatest structural similarity with GPIs anchor reactions by glycosylation regioselectivas with an acceptor diol 1,2-CIS-AXIAL / EQUATORIAL. The study of the biological activities of these pseudodisacáridos and its related phospholipids face fosfolipasas type C and D, support or rule out such structures as potential mediators in the signaling of insulin. Finally, it has conducted a study regioselectividad in glycosylation reactions using an acceptor diólico 1,2-TRANS-DIECUATORIAL derivative D L-CHIRO-INOSITOL analyzing the effect of the shape and nature of the substituents and the acceptor the donor. Within this section has been conducted synthesis of fagopiritoles A1 and B1, natural products of interesting biological relevance.

Author: TORRES SÁNCHEZ M. ISABEL.
Year: 2005.
University: SEVILLA.
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: QUÍMICA ORGÁNICA. FACULTAD DE QUÍMICA. UNIVERSIDAD DE SEVILLA.

Summary: In the first part of this thesis, in his first chapter, describes the synthesis of precursors glicoaminoácidos, compounds containing amino acid structure simultaneously and monosaccharide, and are of great interest biological and pharmacological. There has been a synthesis of several glico-beta-aminoaldehídos of 7 and 8 atoms C with a variety of configurations, from C-glicosil N-bencilnitronas O-protegidas configurations D-glacto-, -xilo- and -ribo- that through cicloadición 1,3-dipolar with vinyl trimetilsilano, leading regional and estereoselectivamente to 3-glico-5-trimetilsilil-isoxazolidinas; distereómeros trained in each case were separated, and his absolute configuration was determined either by X-ray diffraction using NMR. These isoxazolidinas were transformed by treatment with acetyl chloride in the respective glico-beta-acetamidoaldehídos N O-protegidos, enantioméricamente cigars, which are direct precursors of the corresponding glico-beta-aminoácidos chain elongated (7 and 8 C) . It also used the methodology of cicloadición 1,3-dipolar among those glicosil nitronas and another dipolarófilo, methyl acrylate, as a first step regions and esteroselectivo a path toward synthetic counterparts and isomers of castanospermina, a known inhibitor glicosidasas . The 3-glico-5-metoxicarbnol-isoxazolidinas obtained in the cicloadición underwent ring opening of isoxazolidina by treatment with molybdenum hexacarbonilo, leading to gamma-lactamas, whose reduction to the respective pirrolidina, followed by lack of hydroxyl of the party sugar and, in his case, the N atom, finally led to the corresponding products anelación derivatives perhidroazaazuleno (assuming a C-glicosil nitrona configuration D-galacto) or indolizidina (if it has been party nitronas of configurations D-xilo or D-ribo). The structures and absolute configurations of the new compounds were determined by X-ray diffraction in some cases, through special techniques of NMR. The final products are enantioméricamente cigars and, being miméticos of castanospermina have been subjected to enzymatic inhibition studies. In the second part of the thesis, we present the results obtained on a route to the synthesis of a Mimetic a fraction oligosacarídico of capsular polysaccharide (PSC) of Neisseria meningitidis type A bacterium which causes meningitis. In order to minimize the hydrolysis of liaison glicosídico O-fosfato present in the CPs native, was aimed to synthesize the phosphonate similar. It has synthesized a C-disacárido with such source from the penta-O-acetil-D-glucopiranosa through a 1,2-ortoéster bencilado composed key in this methodology. Following the reversal of the configuration at C-2 to get the 3-azido similar configuration D-mano and unprotected from the position anomérica, was obtained for C-glicosil-aleno by treatment with propargil trimetilsilano. The ozonólisis thereof, followed by reduction to alcohol, transforming the group azido in acetamido, and the mesilación and replacement by iodide, would implement the synthesis of Arbuzov to reach the corresponding C-glicosil-metanofosfonato, after serving as a donor in the synthesis of fosfonodisacárido. Starting with the same ortoéster bencilado cited above was obtained a derivative of N-acetilmanosamina as Cbz-amnopropil glycoside and with the hydroxyl at 6 free, which plays a role of acceptor. The condensation of the two in terms of Mitsunobou yielded the desired product. The values of concentrations of inhibition of 50%, compared with Neisseria meningitidis type A of this compound and monosaccharide accept fu 8 eron pro 2b9 metedores in ELISA tests.

Author: FERNÁNDEZ ALONSO MARÍA DEL CARMEN.
Year: 2005.
University: VIGO.
Place of defense: FACULTAD DE QUÍMICAS.
Place of preparation: UNIVERSIDAD DE VIGO.

Summary: Carbohydrates are one of four major classes of biomolecules, along with proteins, nucleic acids and lipids. They constitute the bulk of the organic matter in the soil because of their varied functions in all living things. Normally, carbohydrates are attached to proteins and lipids. More recently, it has been shown that the cell surface carbohydrates involved, so crucial in the process of intercellular recognition. The processes of molecular recognition carbohydrate / protein involved, among other events, the folding and maturation of the glycoprotein in the cell adhesion, in the control of cell growth and other cellular activities, such as embryogenesis, the accession of leukocytes the endothelium delos injured blood vessels, so the return of lymphocytes to their places of origin in the lymph nodes and also in fertilization, which begins with the union of a sperm to a oligosacárido specific surface of the egg. Obviously, the detailed knowledge of the interactions proteínas-carbohidrato involved in biological systems is necessary to understand, and thus be able to intervene rationally in natural processes (fertilization, differentiation, development, maturation, ..) and pathological (infection, inflammation,. .). Because of the enormous potential of carbohydrates for a variety of structures, increasingly is seen as playing a bigger role in the storage and transmission of information between biomolecules (process known as glycocode). Therefore, the elucidation of the mechanisms that determine the disposition of carbohydrates in the recognition sites of enzymes, antibodies and lectin raises great interest. From a general perspective, it is obvious that knowledge of the structural features, dynamic and energy of the complex formed by these biomolecules and carbohydrates is relevant, and to study these interactions with depth is a sine qua non adopting an approximation interdisicplinaria. From a rational point of view, and considering carbohydrates (or its synthetic analogues, glicomiméticos) as potential drugs, it is clear that a detailed knowledge of its structure, both as a free state associated with the receiver is important. The coordinated use of a wide range of biophysical techniques, espectroscopicos and biochemical together with access to oligosaccharides synthetic analogues oligosaccharides (glicomiméticos) and natural or modified protein is of the utmost importance. THE STUDY OF THE STRUCTURAL CONFORMACIÓN OF GLICOMIMÉTICOS LACTOSE ON DISSOLUTION AND INTERACTION WITH A LECTINA IS ONE OF THE TARGETS OF THIS THESIS terms chemical, carbohydrates are molecules polihidroxiladas that, in addition, have non-polar surfaces, aliphatic formed links CH. Therefore, they have a character anfifílico. This property is a real plus having carbohydrates to establish interactions with other biomolecules, because not only can participate in polar interactions, but also are involved in hydrophobic interactions. The links CH located on the same side of carbohydrate, coming in space, may participate in interactions pailimaiento in the side chains of aliphatic and aromatic amino acid protein. These interactions are known as CH. The nature of the interactions CH is still under consideration, although some have been proposed explanations of its stabilizer. On the one hand, has been reported that the movement of water molecules near hydrophobic surfaces is a contribution entrópica favor, and secondly, it has been proposed that the electrostatic interaction between the net positive charge of genetic links CH and the negative charge of the electron cloud ring provides a contribution entálpica also conducive. Probably the polarizabilidad of electrons ring and the polarizing nature of the CH vectors leading to a force attractive. This 8 type ae3 interactions is common in many agencies of the various branches of the evolutionary tree. The enterotoxin Escherichia coli, plant lectin as ricin, algutinina Erythrina corallodendron and several animals galectinas establish interactions between carbohydrates and aromatic surfaces, generally tryptophan. Therefore, it has been proposed that this is the origin of that tryptophan is between amino acids proteinogénicos. THE STUDY OF THE ORIGIN OF THE INTERACTION BETWEEN Rings AROMÁTICOS AND UNITS CARBOHIDRATO AS SIMPLE MODEL OF INTERACTION CARBOHIDRATO-PROTEÍNA IS ANOTHER OF PURPOSE OF THIS THESIS As mentioned above, the molecular recognition carbohydrate protein is the basis of many processes biological, from fertilization to metastases. From a structural point of view, the study of these processes require knowledge of the characteristics of both the carbohydrate as the recipient as well as those individuals in the complex formed. Obviously, knowledge of the factors influencing the possible conformational changes of the isolated associate ligand receptor is essential. Within these factors, it is essential to know the barriers to energy associated with molecular changes, particularly when the recognition process involves drastic changes in the conformation of the sugar in their ground state. One of the cases in which officials have described the existence of distortion in shaping recognized substrates and inhibitors has been in the process of hydrolysis of glycosides by glicosidasas. Recognition of sugar by enzymes glicosidasas is the prelude to the process of catalysis. It has been postulated that ring piranosa sugar must deform to facilitate the breaking of the link glicosídico. In other words, the enzyme must provide a minimum amount of energy through interactions with the substrate, so that it can change its shape. THE STUDY OF ENERGY REQUIREMENTS OF THE DISTORSIÓN OF RING OF EASY SIX ESLABONES, MODELS AS INITIAL PIRANOSAS IS THE THIRD OBJECTIVE OF THIS THESIS

Author: LASO GARCÍA ANTONIO.
Year: 2005.
University: PAÍS VASCO.
Place of defense: FACULTAD DE QUÍMICA DE SAN SEBASTIÁN.
Place of preparation: FACULTAD DE QUÍMICA DE SAN SEBASTIAN.

Summary: In this dissertation is the development of catalytic systems, purely organic and organometallic to conduct training stereoselective reactions links CC, in particular, the reaction nitroaldólica (Henry) and nitro-Mannich (Aza-Henry). It has designed a system based on a catalytic metal salt, a tertiary amine and an aminoalcohol quieral capable of promoting both reactions highly enantioselectiva. Moreover, it has developed a system developer dela reaction aza-Henry under condicones transfer phase, based on the alkaloids of the Cinchona and uses alfam-amidosulfonas as precursors azometinos derived aldehydes enolizables.

Author: Bootello Iglesias Purificación.
Year: 2006.
University: SEVILLA.
Place of defense: Facultad de Biología.
Place of preparation: Facultad de Química.

Summary: This thesis describes the design, synthesis and characterization of the properties of molecular recognition of a new family of mimeticos oligosacarídicos incorporating bridges intersacarídicos type pseudoamida: urea, tiourea and guanidina. The report describes synthetic methodologies for the preparation of monomers multifuncionalizados from which were built glicooligómeros structure diverse: linear and branched dendritic. Have been on the verge effective strategies to access glicooligómeros structures related oligosaccharides of biological interest as lentinan or heptasacárido elicitor of phytoalexins. The analysis of intra-and inter - interactions of glicooligomeros linear model molecules (Me2PO4, Ph PO4) related to DNA and RNA was studied using valuation techniques by NMR water deuterada to establish the structural requirements of these compounds in the molecular recognition.

Author: ALMACELLAS MORENO NÚRIA.
Year: 2006.
University: ROVIRA I VIRGILI.
Place of defense: FACULTAT DE QUIMICA.
Place of preparation: FACULTAT DE QUIMICA. URV..

Summary: The inostilo triphosphate (IP3) is a secondary messenger, responsible for the release of calcium stored in the endoplasmic reticulum, resulting in different cellular responses depending on the cell in which it gives the process. In 1993, isolated from a crop of penicillium brevicompactum two powerful gliconucleósidos trifosfatados, Adenofostina A and B. These are the most potent agonist described so far for the specific recipient of IP3, with affinities 10-100 times the same IP3. It has been described that the substitution of a phosphate group by a group metilencarboxilato isóstero in molecules with biological activity does not alter the recognition of its specific receptors, being more stable compared hydrolysis by phosphatases. Moreover, the introduction of a fluorine atom in a molecule with biological activity represents a major shift in its business, while strengthening the stability of neighboring positions, and thus the entire molecule. This thesis falls within a broader research project, providing the starting point for the same. This project is intended, first, to synthesize different analogues of Adenofostina A in that has been systematically replaced phosphate groups of the molecule original groups metilencarboxilatos isósteros, and on the other hand to introduce a fluorine atom at position 2 " to study the hydroxyl group and replacing essential at the same time strengthen the link glicosídico neighborhood. Firstly have done three different approaches for obtaining synthetic derivative 3,4-dialquilado of glucose. was obtenió the 2'-alil derivative adenosine in six stages synthetic A study of the glycosylation reaction with three different giving glicosilo (fluoride, fosfito and tricloroacetimidato of glicosilo derived from glucose). The best result was with tricloroacetimidato of glicosilo and triflato of terc-butildimetilsililo how activator. however, the performance of this reaction was not very good, so we decided to study a second approximation summarizes where funcionalización end of the molecule was included in the giver and acceptor glicosilo before the glycosylation reaction. one hand was obtained glucopiranósido with the two phosphate groups at positions 3 and 4, thus opening a new avenue for obtaining derived from adenofostina that can be very interesting. But it was not feasible synthetic derivative 2'-metilencarboxilato of adenosine it was an unexpected lactonización. treatment selectflúor a glical protected led to four different giving glicosilo 2-desoxi-2-flúoro-glucopiranósidos very good estereoselectividad and good yields. trial is the glycosylation reaction with a derivative of adenosine protected as acceptor glicosilo, synthesized previously obtained a very good result bromide glicosilo and triflato of plata-carbonato silver as activator system. synthesis continued with the treatment groups protective carrying obtaining synthetic precursor of more immediate the target molecule. Work has opened synthetic routes to get different target molecules and are now continuing synthesis in the laboratory within another doctoral thesis.

Author: OTERO CASAS JOSÉ MANUEL.
Year: 2006.
University: SANTIAGO DE COMPOSTELA.
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: In this dissertation have developed new applications of synthetic carbohydrates leading to the synthesis of inhibitors peptídicos of beta-secretasa, enzyme involved in the development of Alzheimer's disease, as well as the synthesis of benzocarbazoldionas polihidroxiladas, beta amino acids cicloalcánicos polihidroxilados and iminoazúcares graft. The synthesis inhibitors peptídicos of beta-secretasa was based on the application of simple reactions processing delta-lactonas and hexofuranosas in isósteros forming part of the inhibitors. The evaluation of biological inhibitors also obtained was carried out, obtaining interesting results in inhibition of beta-secretasa. In the second part of the thesis developed new applications synthetic nitroazúcares based on the reaction of Michael nucleotide addition to nitroolefinas and in the reaction of Henry intramolecular of nitroaldehídos to generate nitrociclohexanos. The application of these reactions to nitroolefinas from aldohexosas enabled us to establish new methods of synthesis of benzocarbazoldionas polihidroxiladas and beta-aminoácidos ciclohexánicos and ciclopentánicos polihidroxilados, whose novel compound synthesis bean not been described so far. The application of double condensation Henry of nitroazúcares with formaldehyde has enabled us to establish a method for the preparation of iminoazúcares branched five and seven members, with activity as inhibitors glicosidasas, which has also been measured in the course of this work.

Author: HALDER RAJKUMAR.
Year: 2006.
University: PAÍS VASCO.
Place of defense: FACULTAD DE CIENCIAS QUÍMICAS DE SAN SEBATIÁN.
Place of preparation: FACULTAD DE CC QUÍMICAS DE SAN SEBATIÁN (EHU/UPV).

Author: GONZÁLEZ REGO MARIA CONCEPCIÓN.
Year: 2006.
University: PAÍS VASCO.
Place of defense: FACULTAD DE CIENCIAS QUÍMICAS DE SAN SEBASTIÁN.
Place of preparation: FACULTAD DE QUÍMICA DE SAN SEBASTIÁN.

Summary: In this thesis has developed a new methodology reaction aldólica asymmetric based on the Use of Certain chiral ketones derived from camphor own design which allows enolziación direct bearing clouds. Applied aldehydes propargílicos method leads to beta-hidroxiésteres methyl propargílicos with excesses enantioméricos very high. There have also been prepared various cloro- and bromo-cetonas chiral new design has been established and that its application to the reaction of Arzens asymmetric leads to the corresponding esters glicícidos with high estereoselectividad. It has developed a new procedure for the asymmetric reaction Mannich that relies on the use of enolato lytic a alfa-oxicetona chiral derived from camphor and alfa-amidosulfonas as forerunners of N-acil iminas. The oxidative cleavage of cetol leads to beta-aminoácidos essentially enatiopuros. It has been shown that this integrated approach in a carboxylic amino acid coupling, opens a gateway to beta-péptidos and peptides híbridoso alpha and beta.

Author: MARTÍN ORTIZ LAURA.
Year: 2006.
University: MÁLAGA.
Place of defense: FACULTAD DE CIENCIAS DE LA UNIVERSIDAD DE MÁLAGA.
Place of preparation: FACULTAD DE CIENCIAS DE LA UNIVERSIDAD DE MÁLAGA.

Summary: Work performed in the Doctoral Thesis offers a new methodology based on the chemistry of iluros sulfur, led to the synthesis of antibiotics complex type nucleoside Liposidomicinas and Muraimicinas, enzyme inhibitors translocasa I, which operates within the biosynthesis peptidoglycan of the bacterial cell wall. The interest that deserves study, relies on the preparation of a compound common precursor for the synthesis of both the structure cyclical diazepanona present at the Liposidomicinas like compounds which are similar linear very simple Muraimicinas. This compound key, it is a epoxiamida chiral nucleosídica obtained from the condensation diastereoselectiva between iluro sulfur stabilized and a compound aldehídico derived from uridina. For the synthesis of cyclic compounds simple diazepanona was first explored a strategy based on the reaction of aldehyde derivative of uridina with different iluros sulfur funcionalizados to make a subsequent reaction opening regioselectiva intramolecular of peoxiamida formed. An alternative to the synthesis of structure related to both Liposidomicinas with Muraimicinas consisted in the use of epoxiamidas indólicos highly effective for the construction of diazepanonas simple because of the ease with the challenge indólico was shifted pornucleófilos bidentados, occur later, the opening regioselectiva intramolecular ring oxirane. It also conducted the preparation of products cyclic diazepanona configuration 5'S, 6'S, which is deemed to fragment of the natural product of Liposidomicinas through the preparation of a epoxiamida indolínica of cis configuration. Synthetic Studies aimed at the structure of diazepanona containing the funcionalización present at the Liposidomicinas swept various routes such as the displacement delilndol present at the epoxiamidas indólicas by nitrogen compounds funcionalizados, employment of a alilamida nucleosídica as a precursor of a diazepanona functionality simple or application a dihidroxilación asymmetric Sharpless in a fragment previously nitrogen before being mated with an epoxy acid nucleosídico. It also studied the use of chemical delos diazo compounds or 2-amino-1 ,3,4-butanotrioles (ABTs) protected, built from deolefinas trans-sustituídas. Moreover, because of the divergence of the methodology, we set the preparation of analogues Muraimicinas similar to those described in the literature from a epoxiamida chiral nucleosídica derived from indolina. The fundamental problem encountered in this synthesis was oxidation group indólico once the opening of the epoxide with diamina. In addition, products containing the amino group p-metoxibencilo in located in the rest of uracilo, there was an additional disadvantage by not being able to succeed in unprotected from this group at the end of the synthesis. Finally, it was found that it was feasible to conduct a more convergent synthesis to make the openings of epoxide with amines which contain the peptide incorporated.

Author: RODRÍGUEZ LUCENA DAVID.
Year: 2006.
University: SEVILLA.
Place of defense: ESCUELA UNIVERSITARIA DE AQUITECTURA TÉCNICA.
Place of preparation: FACULTAD DE QUÍMICA. UNIVERSIDAD DE SEVILLA.

Summary: The biochemical processes involving phenomena of molecular recognition and complexion that are regulated by secondary structure or higher order presented biomolecules. Therefore, an important aspect of supramolecular chemistry is the design of artificial receptors have been used to achieve development and unnatural oligomers able to take well-defined conformation in solution calls foldámeros, and the preparation of receivers conformacionalmente restricted structure macociclica. Both have been explored in this thesis in order to deepen the interactions involving carbohydrates. Following the first strategy has been prepared receptor type podando derived carbohydrate structure m-xilileno a (tiourea), designed to establish liaison hydrogen interactions by far-reaching and exploring the influence of the formation of structures in secondary phenomena complexation. About foldámeros synthesized have been carried out studies conformational by NMR spectroscopy and dynamics testing of valuation when the anion benzoate as a probe. These studies have shown that groups of oxygenated carbohydrates can act as aceptores in hydrogen bond long-range versus donors pseudoamídicos. The intensity of these interactions and their ability to promote a secondary structure depends strongly on the distance between the centers aceptores and donors and geometry imposed by the structure of carbohydrate. Under favorable conditions, the system xilileno a (tiourea) leads to helical secondary structures and to evaluate the free energy associated with these interactions from the data of thermodynamic intermoleculares complex. Thus, it has been shown that the hydrogen bond of 15 vertices are specially advantaged and has revealed the character modulator of the conformational properties of carbohydrates. The results show a significant parallels with what was observed for natural glycopeptides. In the second chapter of the thesis, describes the preparation of receivers ciclooligosacarídicos based on the disaccharide trehalose (ciclotrehalanas). The use of the group tiourrea as bridges intersacarídico facilitates the synthesis of these compounds and avoids the problems of control esteroquímico associated with the synthesis oligosacarídica. The ciclotrehalanas have a cavity hidrófoba convex, leading into the same side of the hidrógenos beta units sacarídicas thus can be seen as cyclodextrins "inverted". For the synthesis of the various counterparts previously it was necessary to design a strategy for desimetrización of trehalose molecule. From a derivative disimétrico which incorporates functions nitrogenous orthogonal positions on the primary, has developed a modular synthesis which links involve the formation of groups tiourre, allowing obtain ciclotrehalanas sized variables efficiently. It is also possible to transform these groups tiourrea in other groups of type pseudoamida through intermediate type carbodiimida. The strategy developed allows even incorporating elements of nature noglucídica as fragments m or p-xileno. Studies of molecular mechanics and dynamics indicate that the flexibility of ciclotrehalanas increases rapidly with molecular size. However, in aqueous retain a cavity that could include other molecules of appropriate size, as evidenced by the preliminary results of complexation with adamantano 1-carboxilato.