HETEROCYCLICAL COMPOUNDS

Author: BARRIOBERO NEILA JOSÉ ÍGNACIO.
Year: 2003.
University: LA RIOJA.
Place of defense: ENSEÑANZA CIENTIFÍCAS Y TÉCNICA.
Place of preparation: CENTRO CIENTÍFICO TECNOLÓGIGO.

Summary: The main focus of this dissertation is to develop new lines of synthetic track to obtaining derivatives system 7-azabiciclo [2.2.1] hectano and their subsequent use for obtaining products of potential interest. The first addresses the reactivity and synthetic applications of N-Bz-7-azabiciclo [2.2.1] heptano-1-carboxilato of metilo.Cabe highlight the addition of reagents organolitiados as a way to access new a-aminocetonas, preparing radical bridgehead in the system azabiciclo with the inclusion of helogenos and finally interesting synthesis of analogs of ABT - 418 with comprehensive study of its biological activity and behavior theory. It makes the inclusion of the acids N-Boc-3-hidroxi-7-azabiciclo [2.2.1] carboxylic with the hydroxyl group in endo-and exo, as similar conformacionalmente restricted 4-hidroxiprolina. The changes produced by this acquisition, especially in the angle * i +1 and the piramidalización of nitrogen, give grounds to believe that a future inclusion of these amino acids in a sequence peptídico may be useful to study the influence of turns in B the activity of biological molecules such as antagonists of the bradikina. We get so anantiopura four acids 2-hidroxi-7-BOC-7-azabiciclo [2.2.1] heptano-1-carboxilicos.Como intermediate in the synthesis results in the corresponding ketone followed a timely descarboxilación allows obtaining N BOC-7-azabiciclo [2.2.1] heptan-2-onas setting formal synthesis of epibatidina. Lastly, and very successfully addressed the synthesis esterofivergente of carbapenam-3-carboxilatos methyl by controlling the diastereoselectividad in reaction retro-Dieckmann on B-cetroester. Furthermore, it has been confirmed that the value of the optical rotation of trans-carbapenam (3R, 5R) +198.3

Author: SECUNZA SÁENZ DAVID.
Year: 2003.
University: LA RIOJA.
Place of defense: ENSEÑANZAS CIENTÍFICAS Y TÉCNICAS.
Place of preparation: CENTRO CIENTÍFICO TECNOLÓGICO.

Summary: The results at the place that has the dissertation tirulada "(s) and RN-Boc-N, O-isopropiliden-a-metilserinales: use as a precursor product of biological interest," were as follows: I. It has developed a new route sintérica for obtaining both enantiomers of 2-metilglicidol with the hydroxyl group protected by several groups reprentativos-an ether, a mesilo a sililo and éster- based on dihidroxilación asymmetric sharpless (DP) the amide of Weinred acid 2-metilpropenoico. II .- From aldehydes (S) and R -N-Boc-N, O-isopropiliden-a-metilserinales have been synthesized the aminóacidos B y-isaturados a-vinilalanina and a-etinilalanina using this way to the - metilserinal as a building block in reactions tranformación of functional groups. III .- Based on the N - (tert-Butoxicarbonil) -4 metoxicarbonil-2, 2, 4-trimetiloxazolidina, forerunner of a-metilserinal, has been obtained amino acids a-metil-B, B-disutituidos a-metil-B, B-difenilalanina- (aMe) Dip-y a-metil-B, B-dimetilserina- (aME) Dms, apart from a derivative protected from a-metil-B, B-difenilserina- (aMe) Dps-. IV. - Tapping into the behavior of the ring oxazolidina of a-metilserinal as assistant queral have been synthesized all stereoisomers of the a-metiltreonina, thus sought to demonstrate the pervasiveness of this strategy, based on the addition of nucleotide to the aldehyde carbonyl starting at various a-metilserinas B-sutituidas. V. - It has developed a new synthetic strategy that allows quick access through simple reactions to aminoazúcar included in several antibiotics glicopeptídicos 4-epi-L-vancosamina. This has sought to expand the use of a-metilserinal to all kinds of molecules of biological interest and having at its center estereogénico quaternary structure containing methyl amine groups. VI .- Finally, in order to form different a-alquil (or aril) serubakesm has developed a new synthetic route based on the addition nucleófila-1, 2 to double bond CN various imine compounds derived from a-hidroxicetonas . It had obtained a-metilserina with a 74% ee, a-etilserina with a 10% ee And a-fenilserina enantioméricamente pure.

Author: PEREIRA CAMASELLE RAQUEL.
Year: 2003.
University: VIGO.
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTADE DE QUÍMICA.

Summary: We know a variety of heterocyclic compounds, natural and sínteticos with important biological properties, including heterocyclic derivatives as structural elements of ligands certain nuclear receptors. These receptors act as transcription factors regulate gene and host of the process, some of them patólogicos. Therefore, the design, synthesis and subsequent development of new pharmacological ligands modulate gene expression, geared to the discovery of new drugs, it is of great interest. In this paper, we have synthesized several heterocyclic derivatives (thiophene and thiazole) as potential ligands certain nuclear receptors (PPAR And RARA), which could act as drugs against cancer and type 2 diabetes. The methodology developed for the synthesis of these heterocyclic derivatives is based on the introduction of substituents on the ring, quickly and effectively, through two consecutive reactions catalyzed by palladium. Then the funcionalización allows replacement of a third, using two different routes, obtaining receptor ligands RAR or PPAR. This study allows to lay the groundwork for dealing with the preparation of a wide variety d new compounds disustituidos with specific biological properties. Our studies have shown that the position next to the sulfur atom is the most reactive in these derivatives, which allows the first of the desired substituent selectively. In addition, a study has been made mechanistic which allows selectivity observed clarify and determine the nature of the limiting step in this type of reactions catalyzed by palladium.

Author: QUESADA ARMENTEROS ANTONIO.
Year: 2003.
University: JAÉN.
Place of defense: FACULTAD DE CIENCIAS EXPERIMENTALES.
Place of preparation: FACULTAD DE CIENCIAS EXPERIMENTALES.

Summary: By methodology nitrosación selective in the C (5) of aminoalcoxipirimidinas and subsequent aminolisis on 2-amin0-4, 6 (aa) bendloxi-S-nitrosopirimidina has proposed the synthesis of potential inhibitors of AGT (alquilguanina-AND-alquiltransferasa humana), based on núdeo of 2,4-diamino- 6-bendloxi-5-nitrosopirimidina. The choice of amines tested in the reactions of aminolisis, has been carried out in fundon of modificadones presented in the chain alqumca, which fit include: aromatic substituents (aniline), various ramificadones in posidones alpha, beta or gamma the chain alquílica; chains of different lengths (methyl, butil and dodecil), as well as the availability comerdal of them. The methodology found for the reactions of aminolisis is characterized primarily by soft conditions under which occurs sustitudón group bendloxi such as low basicity, moderate temperatures (between 25-60 0c) Ylos good returns. Compounds obtained at different stages of synthesis product line, consisting nitrosated derivatives and compounds undergoing reactions aminolisis have been characterized by various spectroscopic techniques, such as RMNde lH, 13C and 14N, infrared, ultraviolet and mass spectrometry . It has devoted a capítuo full structural analysis using data obtained from X-ray diffraction in monoaistal of nitrosoderivados, some of their precursors and / or similar. The use of this technique and the large number of structures solved has enabled us to perform a detailed structural analysis and molecular supramolecular hadendo use of the orders link and the theory of graphs, enabling electronic molecular patterns for the different types of nitrosopirimidinas studied.

Author: CIRONI LÓPEZ PABLO GABRIEL.
Year: 2004.
University: BARCELONA.
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA UNIVERSIDAD DE BARCELONA.

Summary: The synthesis of high performance parallel both in solution and in solid phase have increased markedly the discovery of new drugs. In this regard our contribution can be seen reflected in this report, setting out different aspects of the above points. It describes the first total synthesis in solid phase of lamellarinas as well as the use of different methods for introducing acids as diverse in the last stage of desanclaje. We have jointly discussed the use of different analytical techniques and what are its scope and its limitations for use in solid phase. Given the importance in quantifying quimiotecas then move to later stages of biological testing, we used the technique most commonly used in organic chemistry 1H NMR for the quantification of the same, using the same, using an internal standard and the other external. The importance and advantages of the solid phase synthesis of small molecules of biological significance heterocyclic are reflected in the synthesis of furopiridinas and furoquinolinas and in the synthesis of 4H-2-3 hidroxi-4-metoxifenil-nafto 1.2 - b piran -1-ona from different bisarilacetilenos, precursors in the synthesis of lamellarinas. Finally reflected an approach to the synthesis of quimiotecas small molecules hetoricíclicas, encompassing both the problems of chemical solution as problematic for the solid phase synthesis of quimiotecas.El scope and limitations of this methodology are discussed in this work.

Author: COMELLES ESPUGA JOSEP.
Year: 2004.
University: AUTÓNOMA DE BARCELONA.
Place of defense: FACULTAT DE CIÈNCIES.
Place of preparation: ESCUELA DE POSTGRADO.

Summary: In this thesis has been optimized and climbed the synthesis of (2R) -2 - (1-adamantil) -2-aminoetanol enantioméricamente cigar. Its synthesis part of ethyl acetoacetate, which introduces the adamantilo in position intercarbonílica. The subsequent transposition Schmidt, hydrolysis and reduction can be obtained 1,2-aminoalcohol racemate. The separation of enantiomers was conducted through its resolution enzyme, which can be obtained for 1,2-aminoalcohol enantiopuro (increased 99% ee). , R) -Adam-Box and (R, R) -Adam-pybox. The chiral ligand (R, R) -Adam-Box has been used in the catalytic asymmetric reaction ciclopropanación and oxidation alílica. The ligand (R, R) -Adam-pybox in reaction hidrosiliación. Both ligands were used in asymmetric catalysis of reaccines of Diels-Alder and Michael. For these reactions, have found some effects of radio inónico metal and impediments estéricos very interesting in the results of the catalysis. Mechanistic studies have been conducted by NMR, UV-Vis and ESI-MS of reaction catalysed by Michael metals. We have found very interesting for intermediate understanding of the mechanism. It has studied the ability of cSA (R, R) -ABTEÂ ® as an agent enantiodiferenciador by 1H-RMN several compounds dicarbonílicos.

Author: BLANCO MARINERO M. PILAR.
Year: 2004.
University: AUTÓNOMA DE BARCELONA.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: ESCUELA DE POSTGRADO.

Summary: Extracts from plants of the family Stemonoacea are rich in compounds known as alkaloids Stemona and have been widely used within the natural medicine China and Japan for the treatment of respiratory diseases such as bronquities and tuberculosis, as well as parasitic diseases. The alkaloids of Stemona are polycyclic and the vast majority incorporated into a skeleton structure of 1-azabiciclo [5.3.0] Dean and one or more rings alfa-metil-gamma-butirolactona. So far synthesized 13 of them, but most of synthesis are long, complex and low yields. In our research group started a few years ago a project aimed at the synthesis of some alkaloids Stemona, using as a key step reaction cicloadición 1,3-dipolar between a nitrona cyclical 5 members and an ester alpha beta-insaturado from 6 carbon atoms conveniently funcionalizado. From an intermediate azabicíclico common pretetende reach different alkaloids group Stemoamida (which have a ring lactoma merged system azabicíclico) and Tuberostemospiromina (presenting a united lactone ring so espiránica). With this goal has been synthesized a new nitrona enantioméricamente pure and intermediate scale multigramo as key to the synthesis of alkaloids. From this nitrona were obtained intermeidos azabicíclicos on which it has tested the formation of the lactone ring espiránico present in alkaloids group Tuberostemospironina, and more specifically the alkaloids stemospironina and stemonidina. The synthesis of stemospironina continuous currently under study, having obtained intermediate whose centers esterogénicos have the same configuration on the alkaloid. In parallel, taking into account the dilemma patent literature on the existence of alkaloid stemonidina, have carried out studies aimed at the synthesis of this alkaloid. Both the lactone espiránica as that found as a replacement ring pirrolina were constructed through a reaction type Reformasky on an aldehyde and ketone, respectively. Based on the results obtained, we can conclude that the structure assigned to stemonidian was misleading and, in all likelihood, the alcoloide is actually stemospironina.

Author: RODRÍGUEZ NUEVO MÓNICA.
Year: 2004.
University: PAÍS VASCO.
Place of defense: FACULTAD DE CIENCIA Y TECNOLOGÍA.
Place of preparation: FACULTAD DE CIENCIAS Y TECNOLOGÍA.

Summary: The reaction aldólica is one of the most versatile tools in the field of organic synthesis in the form links CC, and there are many methodologies developed over the years to carry out this type of process in a way esteroselectiva. One of the most effective is based on the use of chiral auxiliaries united to enolato able to induce selectivity and control, thus the estereoquímica of final products. In this report reflects the results of the study on the possibility of the aminoalcohol pseudoephedrine, which has dmeostrado above its viability in a wide range of processes, including reactions aldólicas with enolatos type propionate (enolatos, alfa-sustituidos) puedar be successfully used as chiral auxiliary reactions aldólicas type acetate (Enolatos not substituted alpha). The tests allow ensure that this auxiliary is effective processes aldólicos type acetate in the presence of chiral aldehydes. However, in reaction not aldehydes aquirales we have seen that the aminoalcohol is unable to control himself during esteroquímico process.

Author: VAZQUEZ VILLA HENAR.
Year: 2004.
University: OVIEDO.
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: In the present report reflects new reactions training carbon-carbon links and carbono-heteroátomo based on the use of reagent tetrafluroborato bis (pyridine) yodonio (R) (IPy2BF4), as a source of ions yodonio. These processes offer an alternative to the use of transition metals to achieve, efficiently and selectively, the preparation of organic molecules. In Chapter 1 describes the synthesis of 2-aril-1-feniltio-2-yodoolefinas by reaction of addiction arenos to feniltioacetilenos in the presence of IPy2BF4. These compounds have interest as selective modulators of the estrogen receptors: in this regard, are the results obtained in preliminary bioassay to establish its biological activity. In Chapter 2 describes the study of the reactivity of systems type alquinil-aldehido face IPy2BF4, in the presence of various nucleotide. Thus, the reaction of o-alquinilbenzaldehídos with alcohols, different nucleotide sililados and arenos leads, so regioselectiva, derived from 4-yodo-1H-benzol [c] pirano through a reaction involving ciclación of carbonyl group on triple link promoted by ions yodonio and catch back of interim results by nucleófilo. Chapter 3 examines the process that takes place when using acetilenos and olefins as nucleotide opposite o-alquinilbenzaldehídos. Thus, it has developed a new method of synthesis regioselectiva of 1-yodonaftalenos and 1-naftilcetonas through a formal reaction of cicloadición cation benzo [c] pirilio with alquinos and olefins, respectively. This methodology has been applied with posteroridad in the synthesis systems heterocyclic benzofusionados, devoting special attention to the synthesis of indoles.

Author: GONZÁLEZ MATILLA JUAN FRANCISCO.
Year: 2004.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: In this dissertation has been performed studying an approach to the synthesis of skeletal pentacíclico present in the tumor antibiotics, more specifically in saframicinas and ftalascidina. Our strategy is different from others because they in the ring piridínico the portion isoquinolínica is formed in one of the last steps in the synthetic process, while we generate one of the first steps. As starting compounds were proposed 3-arilmetilen-2, 5-piperazinodionas, who later underwent hydrogenation various methods N-alquilación/ciclación, that the process was trying versatile to allow any kind of substituents on the ring Ay at position 6. The condensation aldólica / hydrogenation of tricyclic compounds and aromatic aldehydes followed ciclación lowering derivatives thus obtained led to systems pentacíclicos and octacíclicos. It has studied the biological activity of the compounds obtained regarding the ET-743.

Author: HERNANDEZ CUADRADO SUSANA.
Year: 2004.
University: PAÍS VASCO.
Place of defense: FACULTAD DE CIENCIA Y TECNOLOGIA.
Place of preparation: FACULTAD DE CIENCIA Y TECNOLOGIA.

Summary: The present report describes the preparation of pirazolo [1,5-f] fenantridinas, dibenzo [b, f] pirazolo [1,5-d] [1.4] diazepinas and pirazolo [1,5-a] (benzo ) tienoquinolinas, with the key stage of its synthesis forming a link biarílico, Carom-No aril-heteroarílico respectively through reactions catalyzed by palladium. The intermediate allowing access to such systems are polycyclic in all cases pirazoles 1,5-disustituidos prepared through a process tandem exchange amínico / heterociclación between enaminocetonas and hidrazinas. With regard to the pirazolo [1,5-f] fenantridinas training liaison biarílico present in the molecule is made from 1-aril-5- (2-bromoaril) pirazoles under conditions of palladium both homogeneous catalysis as heterogeneous. As alternative / complementary preparation tetraciclo is also able radicalarias. Moreover, for the synthesis of dibenzo [b, f] pirazolo [1,5-d] diazepinas requires the formation of a liaison Carom-N, a process carried out under palladium catalysis of both heterogeneous and homogeneous from 1 - (2-bromoaril) -5 - (2-aminoaril) pirazoles. Finally, in addition to the interest generated products and synthetic sequences employed, it should be noted that the coupling intramolecular catalyzed by palladium leading to systems pirazolo [1,5-a] tienoquinolínico and pirazolo [1,5-a] benzotienoquinolínico takes place between fragments haloheteroarénico and arénico.

Author: ALONSO CARNICERO JOSE MARIA.
Year: 2004.
University: PAÍS VASCO.
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE FARMACIA.

Summary: In this thesis develops synthetic methodology necessary for the preparation of 2H-azirinas resulting oxide difenilfosfina and phosphonate Diethyl through reaction Neber Amended oximes -fosforadas. It also deals with the behavior of these heterocyclic systems against a wide variety of reagents, such as carboxylic acids, amino acids, chlorides of acilo, Grignard reagents, enolatos, heterocyclic amines and thiol. The study of the reactivity of these 2H-azirinas has allowed us to open new routes for obtaining derivatives aminofosforados cyclic and acyclic as aziridinas, pirroles and oxazoles phosphorus, N -cetoamidas, alil and vinilamidas fosforadas, aminofosfonatos ... Likewise have spread synthetic methodologies previously developed to obtain new derivatives aminofosforados with fluorinated substituents, given the growing importance of fluorinated compounds in Medical Chemistry. Finally, it has developed the synthetic methodology necessary for the preparation of analogues fosfomicina derivatives oxide difenilfosfina using (S) -lactato Ethyl as chiral auxiliary.

Author: GARCIA GARCIA EVA.
Year: 2004.
University: PAÍS VASCO.
Place of defense: FACULTAD DE CIENCIA Y TECNOLOGIA.
Place of preparation: FACULTAD DE CIENCIA Y TECNOLOGIA.

Summary: In the research work that is reflected in this report is a study of the estereoselectividad 'reactions? -amidoalquilación Intramolecular and conjugate addition, the synthesis - oriented systems pirroloisoquinolínicos and benzoquinolicidínicos. On the one hand, the sequence has been applied addition nucleófila-ciclación via ion N-aciliminio the asymmetric synthesis of pirroloisoquinolinonas, from N-fenetilsuccinimidas enantioméricamente pure from L-DOPA. It has studied the effect of substituents for a center estereogénico in? The nitrogen on the estereoselectividad 'reactions? -amidoalquilación Intramolecular, varying the type of acid used in the generation of ion N-aciliminio intermediate. Moreover, it has been investigated estereoselectividad the reaction of conjugate addition of organometallic reagents on the unit lactam?? -insaturada Of tetrahidrobenzo [to] quinolicidonas. Additions have been made conjugate of organocupratos as well as stabilized by nucleotide sulfur, salts such as lithium derivatives ditioacetálicos or stabilized by conjugation? As the sodium salt of dimethyl malonate. It has been established that these reactions are conjugate addition, in general, highly diastereoselectivas, which has helped prepare various hexahidrobenzoquinolicidonas polisustituidas. In addition, we laid the groundwork for opening a new procedure for synthesis of alkaloids type Emetina.

Author: LOINAZ BORDONABE IRAIDA.
Year: 2004.
University: PAÍS VASCO.
Place of defense: FACULTAD DE CIENCIAS QUIMICAS.
Place of preparation: FACULTAD DE CIENCIAS QUIMICAS.

Summary: It has been shown that strong autoagregación that solvents fluorosos have many amides, carbamates, ureas,? -aminoácidos Protected and peptides can be prevented by training bridges hydrogen heteromoleculares with perfluorinated carboxylic acids in length average. Thus, it has succeeded for the first time to substantially increase the solubility of compounds amídicos in solvent fluorosos without increasing the size of strings fluorosas united covalentemente to them. According to the evidence presented NMR and IR has been shown qualitatively so that the bridges of hydrogen heteromoleculares trained in pairs amide / acid are strongest solvents fluorosos that not Coordinating organic solvents, such as CH2Cl2 or CDCl3, and supramolecular corresponding entities are formed only in the media fluorosos. Furthermore, it describes for the first time that the ratio repartote several ureas fluorosas between perfluorohexano and organic solvents can be drastically altered by the addition of quantities estequiométricas acid perfluoroalcanóicos medium chain. This phenomenon has been applied to a new procedure for non-extractive chromatographic purification of peptides and esters disabled, obtained by synthesis peptídico a carbodiimida fluorosa. Moreover, it has been shown that introducing a fragment? -amino-? -bencil-? -lactama A ciclopéptido RGD formula cycle (Arg-Gly-Asp-? -Lactam-Gly) Does not induce an effect betágeno but gammágeno, resulting in aqueous formation of a system of hydrogen bond intramoleculares in which a strong inverse gamma shift between NH (? Lactam) and CO (G1y2). That ciclopéptido presents a high-powered as inhibitor integrina? V? 3 which confirms the hypothesis of "separation of elements restriction conformacional and appreciation" made by us and validates the design of new ciclopéptidos RGD based on that principle.

Author: RUIZ FERNANDEZ JAVIER.
Year: 2004.
University: PAÍS VASCO.
Place of defense: FACULTAD DE CIENCIA Y TECNOLOGIA.
Place of preparation: FACULTAD DE CIENCIA Y TECNOLOGIA.

Summary: The present research work has been studied ciclación intramolecular compound aril - heteroaril-litio generated by exchange litio-halógeno, also known as ciclación Parham. This has been synthesized in various heterocyclic systems that have been varied systematically halogen employee, electrófilo internal need for ciclación, the size of the new ring formed, the system aromatic post at stake and the pattern of replacing it. We have opened up in this way, new ways of synthesizing pirrolo [1,2-b] isoquinolonas, pirrolo [1,2-a] benzo [d] azepinonas, pirrolo [1,2-a] benzo [d] azocinonas , and different systems indolicidinicos heterofusionados.

Author: MONT CASELLAS NÚRIA.
Year: 2004.
University: RAMÓN LLULL.
Place of defense: ESCOLA TÉCNICA SUPERIOR INSTITUT QUÍMIC DE SARRIÁ.
Place of preparation: ESCOLA TÉCNICA SUPERIOR INSTITUT QUÍMIC DE SARRIÁ.

Summary: Protein Quinasas (PKs) are involved in processes as diverse as angiogéneses, restenosis, arterisoclerosis, particularly in the processes of tumor growth. Accordingly, the development of selective inhibitors PKs has become a very active area of research. In this environment, described a multicomponent reaction, assisted by microwave, for the synthesis of pirido [2,3-d] pirimidinas 4-amino or 4-oxo replaced, which provides some high yields in response times of 10 minutes. It also describes a method for the synthesis of 4-cloropirido [2,3-d] pirimidinas or hydrogen or carbon substituents at position C2 by ciclación with hydrogen chloride from 2-acilamino-3-ciano-6-oxo-1 , 4,5,6 - tetrahidropiridinas, followed by treatment with POC13 of systems pirido [2,3-d] pirimidínicos 4-oxo replaced resulting. It has been designed, selected and synthesized by the reaction multi earlier, a quioteca inhibitors potential PKs structure 2,4-diaminopirido [2,3-d] pirimidínica substituted nitrogen linked to carbon C2. It describes the acilación selective nitrogen exocíclico system pirazolo [3.4, - b] piridínicos, and uses this method for the synthesis of a quicioteca structures 3-acilamino-3-pirazolo [3,4-b] piridínicas as potential Inhibitors of Protein Quinasas.

Author: MACHO MAQUEDA SONIA.
Year: 2004.
University: BURGOS.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: The study of heterocyclic systems is one of the branches of the Organic Chemistry most arouses interest due to their presence in most natural products known for their potential applications as new materials. In this thesis has been performed the synthesis of new systems heterocyclic sulfur and / or nitrogen, and the study of some of its properties that may make them susceptible to being used as raw materials. The synthesis of these new hetero had as a basis the use of chlorides sulfur and nitrogen organic reagents. First, it has deepened in the synthesis of hetero nitrogen and sulfur from cetoximas. The agents carrying sulfur chlorides have been used sulfur. The reactions between these two reagents heading in the presence of tertiary amines have enabled the development of new systems that include one or two rings [1,2,3] ditiazol in their structures, some of which include an additional heterocyclic ring, as for example pentatiepina or [1.2] tiazina. Using 1-aminocicloalquenonitrilos in this kind of reactions has been shown to be a new route of synthesis of such compounds: [1,2,3] ditiazoles, isotiazoles and especially [1,2,6] tiadiazinas. The tiadiazinas prepared shown to possess some interesting physicochemical properties that bring extra interest as potential new materials. For example, one has characteristics typical of a liquid crystal termótropo. Another of the ways of synthesizing hetero is changing the -acilaminocarboxamidas obtained in the reaction of Ugi. The reactive nitrogen in this case are isonitrilos and primary amines. The basic treatment products Ugi prepared from carboxylic acids funcionalizados (trichloracetic acid, acid cianoacético and acid cloroacético) has brought out the development of various systems such as nitrogen hydantoins, pirrolidonas, -lactamas and succinimides.

Author: MACIAS RABANAL ALBERTO.
Year: 2004.
University: OVIEDO.
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: This report describes the preparation, study of reaction mechanism and applications of new synthetic compounds beta-lactámicos. In Chapter 1 is listed synthesis diastereo- and enantioselectiva new beta-lactamas espiránicas from pirrolidina, tetrahydrofuran and piperidina through reaction cicloadición [2 +2] between cetenos cyclical and iminas. The theoretical study conducted allows us to justify the results estereoquímicos obtained. It also describes the preparation of beta-aminoésteres and beta-amoniácidos genialmente disustituidos derived from these beta-lactamas espiránicas. In Chapter 2 discusses the applications of synthetic cis 4-fonil espiro beta-lactamas from pirrolidina and piperidina as substrates of departure for obtaining 1,4-diazabiciclo [4,3,0] nonan-5-onas and 1.4-diazabiciclo [4,4,0] decan-5-onas respectively. This methodology has been applied to the preparation of biologically active compounds as sigma receptor ligands. Furthermore, it describes the theoretical study of the mechanism of the reaction. In Chapter 3 describes the synthesis and resolution of new beta-lactamas espiránicas from pirrolidina similar nocardicinas and monobactamas, as well as their application to the preparation of beta-aminoésteres and beta-aminoácidos geminalmente disustituidos. These units have been used as a basis for the preparation of alpha and beta, beta-péptidos the potential to adopt secondary-type helical structures. In Chapter 4 is listed synthesis diastereo- and enantioselectiva new systems that incorporate a tricyclic ring beta-lactámico merged with a 1,4-benzodiazepina on his face d by the reaction of cicloadición [2 +2] ceteno-imina . Using cetenos cyclic derivatives pirrolidina and tetrahydrofuran allows us to access the corresponding systems tetracyclic espirámicos. It has also developed the methodology necessary to access similar tri-and tetracyclic N-no replaced.

Author: GARCÍA ROMERO MARCOS DANIEL.
Year: 2004.
University: SANTIAGO DE COMPOSTELA.
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: The current anti-neoplastic and antiviral therapies are based, in large part, on the use of nucleoside analogues. Of the 19 drugs approved so far for the treatment of infections caused by HIV, 11 are nucleoside analogues. Foremost among these are the nucelósidos carbocíclicos or carbonucleósidos that arise by replacing oxygen in the ring of sugar by a methylene group. The present paper describes the exploration of synthetic routes leading to carbonucleósidos where the double bond in position 2'-3 'of the molecule carbovir prototype has been extended to a structure azoloncodensada type aromatic, on the idea that these changes could on the one hand modulate lipofília of the plateau region of the structure, as well as improve their interaction with viral enzymes. In this context, we examined two types of routes leading to synthetic compounds of this type or precursors thereof. Such routes have been used in practice for the synthesis of 1'-homoderivados of nucleoside analogues carbocíclicos of derivatives structure ciclopenta [c] pyrazole. These compounds have been evaluated to determine its activity on DNA viruses and retroviruses and for the determination of their cytotoxicity in vitro. Of the eighteen compounds evaluated biologically, only two of them have submitted some evidence of activity against the virus Varicella Zoster and Cytomegalovirus.

Author: ALVARADO NARVÁEZ MARIO HERNÁN.
Year: 2004.
University: SANTIAGO DE COMPOSTELA.
Place of defense: FACULTAD DE FARMACIA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: The search for new structures with neuroleptic activity is a subject of great interest in design programs and drug discovery developed by the scientific community. The preparation of organic molecules with pharmacological activity and specific emphasis on the study of the structure-activity relationship is within the chemistry of drugs, a topic of great interest to the discovery and development of new drugs used to treat some CNS diseases such as schizophrenia. The present report describes the synthesis and characterization of aminovalerofenonas and aminobutirofenonas heterocyclic conformation and restricted their studies affinity for receptor dopmaminérgicos D2 and serotonin 5-HT2A and 5-HT2C. The study of drug binding to receptors of these new families aminobutirofenonas conformation restricted and their senior counterparts (amonovalerofenonas) has enabled us to make a significant contribution to knowledge of the relationship estructura-afinidad in these compounds.