ORGANIC CHEMISTRY (2)

Author: RODRÍGUEZ ACEBES RAQUEL.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE CIENCIAS QUÍMICAS.
Place of preparation: FACULTAD DE CIENCIAS QUÍMICAS , UCM.

Summary: SUMMARY: In this paper we raised simple and flexible giving access to different structures merged and espiránicas from 13-lactamasy oxindoles using the same synthetic approach, consisting of processes addition nucleófila the carbonyl group and the subsequent ciclación of adducts resulting. So, have studied the reactions of alilación, bromoalilación, propargilación, alenilación and butadienilación of 2,3-azetidindionas, 4-oxoazetidin-2- carbaldehídos and 2,3-indolindionas. These processes have been promoted by metals in aqueous medium and has been occurring on a regional and esteroselectiva under optimum conditions. This has spread the methodology developed previously in our working group to 13-lactamas. Alcohols bromohomoalilicos alquenilsustituidos were subsequently used to synthesize so stereoselective systems B-lactámicos biciclicos highly funcionalizados through reactions cielación radicalaria or coupling intramolecular Heck. We have prepared compounds espiránicos united structures oxindólicas or B-lactámicasde form stereoselective with great structural variability from unsaturated alcohols from 3-oxo-B-lactamase isatinas. Para ello se han llevado a cabo reactions metátesis closure ring, cielaciones Heck and processes ciclación intramolecular of a-alenoles in the presence of transition metal. then bis-azetidinonas resulting in preparing bis-B-aminoésteres conformacionalmente restricted by selective hydrolysis liaison amidico ring Beta-lactámico.

Author: LOPEZ GARCIA MONICA.
Year: 2004.
University: OVIEDO [www.uniovi.es].
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: It has been shown in recent years that the use of bioctalizadores in organic synthesis, is an extremely important alternative to the conventional chemical catalysis, especially for the preparation of compounds enantioméricamente cigars. In this report, structured into three chapters, has been carried out the resolution and desimetrización different compounds difuncionales through enzymatic reactions of acilación, aminólisis and amonólisis. Furthermore, it describes the implementation of some of the products obtained in chiral synthesis of compounds of biological interest. CHAPTER 1 was developed a synthesis quimioenzimática highly effective indanos 1,3-difuncionalizados enantiopuros. The corresponding cis-and trans aminoalcoholes N-protegidos solved acilación enzyme using CALB as biocatalizador. With this methodology are available all possible isomers form enantiopura and with very good yields. The utility of these compounds is shown through the preparation of cis-and trans indan-1 ,3-diaminas ortogonalmente protected through a reaction Mitsunobu. The total investment of the configuration during the reaction Mitsunobu evidenced by the combination of techniques NMR and molecular modeling. The usefulness and versatility of the strategy is demonstrated with the last unprotected selective each amino group in mild reaction conditions and high yields. CHAPTER 2 is studying the desimetrización different glutaratos proquirales through aminólisis and amonólisis enzyme, remain nuevola CALV the biocatalizador more effective. Regardless of the structure of the substrate, the lipase shows preference to the group pro-R thereof, obtaining always amidoéstres configuration S. In no case has been detected formation diamidas. However, the excesses enantioméricos and yields largely depend on the polarity of the group at position 3 of diéster departure. CHAPTER 3 Describes a new synthesis quimioenzimática acid (R) -3.4 -diaminobutanoico. This process included as a key step Hofmann rearrangement of amidoéster obtained in the amonólisis enximática of 3-(bencilamino) glutarato dimethyl. Stages simple protección-desprotección also allow the preparation of a derivative ortogonalmente protected acid (R) -4 - (N-Boc) -3 - (N-Fmoc) diaminobutanoico. Moreover, it has demonstrated the application of this resulted in the synthesis of peptides in solid phase, in particular on the preparation of new aza-miméticos RGD with potential therapeutic activity. Some of the results obtained in this study are listed in the following publications: "Synthesis of (R) -3.4 -diaminobutanoic acid by desymmetrization of dimethyl 3-(benzylamino) glutarate through enzymatic ammonolysis" M. López, I. Alfonso V. Gotor J. Org. Chem 2003.68 648. "Desymmetrization of dimethyl 3-substituted glutarates through enzymatica ammonolysis and aminolysis reactions" M. López, Alfonso I, V. Gotor Tetrahedron: Asymmetry 2003.14603. "Synthesis quimioenzimática of (+) and (-) -cis, (+) and 8-) -trans-3- (N-benciloxicarbonilamino) indan-1-ol, (+) -cis-1- (N-benceno- 1.2-dicarbonil) amino-3- (N-benciloxicarbonil) aminoindano, (+) and (-) -trans-1- (N-benceno-1 ,2-dicarbonil) amino-3- (N-benciloxicarbonil) aminoindano "M. López, I. Alfonso V. Gotor P2000302536. "Hyghly efficient biocatalytic resolution of cis and trans-3aminoindan-1-ol. Syntheses of enantiopure orthogonally protected cis and trans-indane-1 ,3-diamine" M. López, I. Alfonso V. Gotor Chem.Eur.J. 2004, 10, 1. "Chemoenzymatic approach to a (R) -3.4 -diaminobutanoic acid derivative with a suitable orthogonal protection for solid phase peptide synthesis" M. López, I. Alfonso V. Gotor Letters in Organic Chemistry 2004, 1, 254.

Author: LEVY LAURA MARIANA.
Year: 2004.
University: OVIEDO [www.uniovi.es].
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: Of the biocatalysts used in organic synthesis, Lipases are enzymes more effective in resolving mixtures racémicas. Through processes enzymatic hydrolysis, esterification, transerificación, transesterificación or aminólisis, it is possible to prepare alcohols, acids, ethers or amines enantiopuras. In recent years, the enzymatic resolution of alcohols with lipases in organic solvent, has proved to be the most popular process for the preparation of alcohol and varied structures with a high optical purity. In this report, structured into three chapters, describes the production of three different types of sintones chiral, lipases using organic solvents through d processes transesterificación. Furthermore, in some cases it has been carrying out a systematic study sobrelos different parameters that influence such processes. The first chapter has been divided into two parts, the first resolution has been studied via O-acetilación enzyme cis and trans-beta-hidroxiesteres cyclic 5 to 7 members using lipases of Candida antarctiva A and B, having obtained excellent enantioselectividades in every case, which has allowed the twelve isolate potential eesteroisómeros so enantiopura and with high yields. The second part has carried out a more detailed study of the enzymatic resolution of cis-and trans-beta-hidroxiesteres cyclical using molecular modernization. The results of this study showed that the conformation preferential taken by the cyclic alcohols departure is one of the most important determining factors of the reactivity of these, compared to acilación catalysed by CAL-B. In the second chapter, has extended the methodology developed in the previous paragraph, applying it to the resolution of beta-hidroxinitrilos cyclical alpha alfa-disustituidos of 5 and 6 members through Da reaction O-acetilación enzyme, getting excellent again enantioselectividades and yields, in this process must be emphasized that gets quiralidad on a center estereogénico quaternary. In turn, a study of different reducers, have been synthesized these substrates in a manner diastereoselectiva. By calculations of conformational cycles has been studied qualitatively explain the differences in reactivity exhibited by the CAL-B in acilación of these compounds. Finally, in the third chapter, has been carried out resolving cis and trans-3-aminociclohexanoles cyclical N-protegidos. The modificaicón certain parameters reaction, as the solvent, the rate biocatalizador and the group N-protector, has made it possible to isolate these compounds with high enantioselectividades and yields. It has also studied the influence of the group N-protector and delas conformations adopted by these substrates, can reach a qualitative explanation for the different results obtained.

Author: CORTÉS BAREA NURIA.
Year: 2004.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: UNIVERSIDAD DE BARCELONA. FACULTAD DE QUÍMICA.

Summary: The focus of the thesis focuses on the use of combinatorial techniques to design and synthesize a quimioteca of peptoides. The peptoides are a type of peptidomiméticos whose general structure is based on a skeleton of glicinas N-sustituídas. Its structure is well-suited to implement the strategy of combining positional tracking for solid phase synthesis. These compounds have a great interest in the biomedical field. Thus, screening of the quimioteca of peptoides face different biological targets of therapeutic interest has led to the identification of two powerful neutrilizadores of MDR phenotype in the area of cancer, as well as two potent inhibitors of LPS in the area of shock septic. These compounds have provided a starting point for the optimization of structures to design new compounds that are at most activity and selectivity meet its targets. Moreover, it has carried out the optimization of a process to obtain peptoides with one end terminal carboxylic (peptoides acids) with the aim of being able to connect these compounds to solid supports such as columns were farosa or agarose, and to biotinilizarlos and acoplarlos to agarose columns with guesses. With this type of columns with peptoide inmobilziado has used the technique of affinity chromatography to identify potential targets of a peptoide a protein extract containing proteins of different nature. The study to obtain peptoides acids has led to the approach of two new quimiotecas based on an overall structure of peptoides dimers and peptoides dímeros-cíclicos, to be held in the near future in our research. Such molecules can be very interesting interaction studies proteína-proteína.

Author: VILA PERELLÓ MIGUEL.
Year: 2004.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAT DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA-UNIVERSIDAD DE BARCELONA.

Summary: The alarming increase in the number of pathogens resistant to one or more antibiotics is one of the major health problems of today. The antimicrobial peptides, genetically coded components and systems innate immunity of most living things have been postulated over the past few years as a plausible alternative to conventional antibiotics. These hopes are based on the particular mechanism of action that makes them less likely to give rise to resistant strains. This thesis has been carried out studies of structure activity relationships on two antimicrobial peptides vegetable rich in cysteine - thionin of Pyrularia pubera (PpTH) and heveina as representative members of the active peptides against membranes and interacting with chitin respectively. The tioninas are the first families of antimicrobial peptides to those described in vitro activity against pathogens and ran playing a role in the defense system of plants. In this work we have developed synthetic strategies based on the synthesis of peptides in solid phase and the oxidative folding to obtain good yields PpTH, a peptide of 47 amino acids and 4 bridges disulfide. It has also developed a method for the characterization of the connectivity between Cys in this family of peptides based on partial reductions and cianilaciones. The structure activity studies have identified the cause structural double helix antiparalela central PpTH as responsible for their activity. Finally, we have used each of the two propellers that constitute this structural reason to develop new antimicrobial agents through the introduction of a bridge disulfide no-nativo to stabilize the active conformation, these peptides floor exhibit a powerful antimicrobial activity comparable to that of the thionin native. The structural dissection of the herveina has been conducted based on the three-dimensional structure of the complex with quitooligosacridos that the C-terminal region of the peptide is not directly involved in the recognition process. There has been described peptides of the family of heveina with fungicidal activity acknowledged that lack of this C-terminal end, taking all this in mind we decided to synthesize a peptide corresponding to the extreme N-terminal minimum of heveina (HEV32) to assess their affinity toward quitooligosacáridos. The structural studies and affinity by NMR showed that HEV32 recognized that virtually identical to that of heveina to quitooligosacáridos and can be regarded as a domain structurally and functionally autonomous. Finally, and given the current strong interest in the development of suitable methods for the study of interactions proteína-carbohidrato we have developed a new approach to the grounding of sugars in solid surfaces and have demonstrated their usefulness for studying the interaction lectin with quitooligosacáridos using resonance of plasmón surface (SPR).

Author: MOLINOS GÓMEZ ALBERTO DOMINGO.
Year: 2004.
University: BARCELONA [www.ub.es].
Place of defense: FACULTAT DE QUÍMICA.
Place of preparation: FACULTAT DE QUÍMICA.

Summary: We have developed a number of synthetic methodologies for obtaining new cromóforos organic nonlinear optical properties, based on acridinas asymmetrical replaced. Their properties have been identified for generation of a second harmónico of radiation incident, and has been able to demonstrate the effectiveness of the synthesized molecules, in particular the appropriateness of the use of 6 - (2-aminobenzotiazolil) -2-nitroacridinas due to the increase in the efficiency of second harmonic generation by the positive effect that causes the balance tautomérico. Have been synthesized in the same way systems azacorona-acridina ONL and have identified the potential modulation of the optical properties of these molecules by the complexation of different metals - has been made by another party approaches to the synthesis of polymeric systems for the complexation with metals coordination octaédrica. Moreover, it has developed an efficient method for linking cromóforos ONL, among them similar to those cromóforos described above by adding a feature wall, the surface of polymeric microspheres which are part of an emulsion, which is suscpetible to form a system crystalline coloida with behavior glass fotónico. With this method has been improved efficiencies generating harmonic radiation incident of this type of crystals fotónicos in more than three orders of magnitude with respect to similar systems described so far. Lastly, there have been approaches to the synthesis of organic radicals stable molecules with high-capacity generating states of charge transfer, as acridinas or benzotiazoles, in order to obtain organic systems with macroscopic properties ferromagnéticas.

Author: JONH JAIRO MÉNDEZ ARTEAGA.
Year: 2004.
University: LLEIDA [www.udl.es].
Place of defense: UNIVERSITAT DE LLEIDA.
Place of preparation: UNIVERSITAT DE LLEIDA.

Summary: The biocatalysts, both enzymes isolated as whole cell (resting cells), are known for their efficiency as biocatalysts of chemical processes. Its properties regions and estereoselectividad well as its application in organic solvents have made them important tools in organic synthesis. Several applications in different areas of the productive sector showed its importance and potential in the food industry, petrochemical and fármaco-química. The central theme of this thesis study has been implementing a biocatalizador, obtained from a strain of Rhizopous oryzae, in the preparation of derivatives of polyols. This has been first to identify a set of basic kinetic parameters of this biocatalizador. Later the same has been applied to the transformation of traicilglicéridos and esters clorohidrinas. Transforming traicilglicéridos has been studied directly on different materials oilseeds. For its part, the transformation of esters clorohidritnas has allowed the preparation of (R) -4-cloro-2-butanol an ee of 98%. The preparation of these esters clorohidrina has been carried out through a reaction with clorotrimetilsilano, reaction developed in the laboratories of chemistry at the University of Lleida and on the thesis that it is also introducing new data seem to confirm that the mechanism proposed in its day

Author: GUTIERREZ RODRÍGUEZ MARTA.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE CC. QUÍMICAS.
Place of preparation: FACULTAD CC. QUÍMICAS.

Summary: That argument falls in the field of Medical Chemistry, and raises the use of structures espirolactámicas [4.4], miméticas of beta type II turns of the secondary structure of peptides, for the restriction conformacional and studying l as bioactive conformation of the depsipéptidos tumor aplidina and tamandarina A and tripéptido neuroprotective Gly-Pro-Gly (EPG), as a first step toward the design of miméticos with appropriate pharmacokinetic properties. For conservation objectives has been undertaken optimized synthesis of new structures espirolactámicas and subsequent insertion into the sequence of each of the peptides goal, using organic synthesis methodologies and synthesis of peptides in solution. He then has been carried out analysis conformacional of the most significant compounds each of the families of similar peptídicos goal by NMR techniques and molecular modeling. Finally, it has been determined the cytotoxic activity of the new analogues didemninas synthesized and activity in vitro neuroprotectora analogues PGE. In each case, the correlation of results with biological analysis conformacional have drawn conclusions on the conformations of bioactive peptides natural model.

Author: RODRÍGUEZ RANERA CAROLINA.
Year: 2004.
University: COMPLUTENSE DE MADRID [www.ucm.es].
Place of defense: FACULTAD DE CC. QUÍMICAS.
Place of preparation: FACULTAD DE CC. QUÍMICAS. UNIV. COMPLUTENSE.

Summary: This paper has tried to contribute to the development of new synthetic methodologies for the preparation of beta-lactámicos bicíclicos and polycyclic systems structurally novel. They have studied various strategies that combine reactions carbonil-énicas processes cicloadición of Diels-Alder in both ca those in their international variants and intramoleculares. Also, in some cases, has used the methodology of free radicals to access beta-lactamas fused rings to eight nine links. Moreover, as a contribution to the strategy of sintón beta-lactámico, have used different 2-azetidinonas funcionalizadas for the synthesis of tetrahidroazocinonas, nitrogen products of synthetic and biological interest. This report has been structured into five chapters. In Chapter I provides an overview of the main antibiotics beta-lactámicos synthesis methods and their most significant, as well as the most important applications of 2-azetidionona in the field of Organic Synthesis. In Chapters II, III and IV describes the use of 2-azetidinonas as molecular building blocks in asymmetric synthesis of different nitrogen compounds of biological interest, such as alcohols homoalílicos monolactámicos derivatives carbacefam funcionalizados and beta-lactamas tricíclicas and you tracíclicas structure unconventional. Finally, in Chapter IV deals with the preparation of tetrahidroazocinonas funiconalizadas by transposing Cope of 3,4-dialquenil-2-azetidinonas, which represents the first example of this reaction in which the link C3-C4 kernel beta-lactámico it is the central point of contact system 1,5-hexadiénico.

Author: DIAZ OLTRA SANTIAGO.
Year: 2004.
University: JAUME I DE CASTELLON [www.uji.es].
Place of defense: E.S. TECNOLOGIA Y CIENCIAS EXPERIMENTALES.
Place of preparation: E.S. TECNOLOGIA Y CIENCIAS EXPERIMENTALES.

Summary: After two chiral ketones derived from carbohydrate (S) -eritrulosa a alfa-sililoxicetona and etilcetona, has studied the addition of their respective enolatos boron to a series of aldehydes alfa-quirales (separated into two groups, alpha metilaldehídos and alfa-alcoxialdehídos). The results were equivalent to the two chiral ketones, additions aldólicas were totally diastereoselectivas with the two enantiomeros of alfa-metilaldehídos, thereby increasing the usefulness of this synthetic methodology, and were totally diastereoselectivas with only one of the two enantiomers (S ) of alfa-alcoxialdehídos, with the addition to alfa-alcoxialdehídos configuration A little diastereoselectiva and giving options to patterns of decomposition. Adding Z-enolato boron in the alfa-sililoxicetona a alfa-alcoxialdehído configuration S has been used to carry out and stereoselective total synthesis of naturally occurring lactone (+) -anamarina. It has also been used adding Z-enolato boron in the etilcetona a alfa-metilaldehído to synthesize the fragment C1-C9 of sorafeno A, a macrolide with a potent antifungal activity.

Author: DIEGUEZ VAZQUEZ ALEJANDRO.
Year: 2004.
University: OVIEDO [www.uniovi.es].
Place of defense: FACULTAD DE QUIMICA.
Place of preparation: FACULTAD DE QUIMICA.

Author: SUAREZ ALVAREZ JOSE RAMON.
Year: 2004.
University: OVIEDO [www.uniovi.es].
Place of defense: FACULTAD DE QUIMICA.
Place of preparation: FACULTAD DE QUIMICA.

Author: JIMENEZ GONZALEZ LETICIA.
Year: 2004.
University: ALMERÍA [www.ual.es].
Place of defense: FACULTAD DE CIENCIAS EXPERIMENTALES.
Place of preparation: UNIVERSIDAD DE ALMERIA.

Summary: The pterocarpanos, natural compounds type isoflavonoide, are characterized by interesting biological properties. Notable by their strong activity fitoalexínica, but now its scope has been extended to other important activities (antitumor, antiviral, antiparstaria or as an antidote to snake venom). In this thesis has been to point to a new strategy for the synthesis, in a convergent and diastereoselectiva of such compounds. The synthetic approach designed basically consists of two key steps. The formation of benzoxasilepinas by metátesis intramolecular of olefins and the subsequent acquisition of ring dihydrobenzofuran by reaction Sakurai amended. Finally, the formation of the skeleton pterocarpano carried out by ciclación under the conditions of reaction Mitsunobu. This method consists of 8 stages of reaction and provides an overall performance of 11-16%, from simple commercial products. Finally, it has made an initial approach to the synthesis enantioselectiva of pterocarpanos by studying Sakurai at its asymmetrical version.

Author: SANCHIS MARTÍNEZ JOAQUÍN.
Year: 2004.
University: VALENCIA [www.uv.es].
Place of defense: Sala de Grados Facultad de Farmacia.
Place of preparation: FACULTAD DE QUÍMICA. UNIVERSIDAD DE VALENCIA (ESTUDI GENERAL).

Summary: The objective of this thesis was the synthesis of compounds that provide interesting properties as ligands capable reconnaissance and selective complexation Transition metal toxic. There have been three major families synthesize compounds aza-podandos derivatives 2.2 'bis (aminocarbonil) -4.4' -dinitrobifenilo, 2.2 'bis (aminocarbonil) -4, 4'-bis (dimethylamino) - biphenyl and 2.2 'bis (aminometilen) -4.4' bis (dimethylamino) -bifenilo. They also have synthesized a series of ligands structurally similar to podandos earlier, but containing azacoronas, and a number of other ligands similar but without any additional functional group in chains. The latter were prepared to be used as compounds in the pattern of fluorescence studies. Compounds obtained, may be divided into 3 major series. The series I is the diamidas possessing nitro groups in the positions 4.4 '. These compounds are prepared from acid difénico and amines suitable for each case as a reaction formation amides type Schotten-Baumann. The series II is synthesized from the reduction of nitro groups to dimethylamino through a reduction with hydrogen and a catalyst of palladium in the presence of formaldehyde. Finally, the reduction of the amide with diborano and THF leads to obtaining Series III products. Subsequently, we studied the behavior of these ligands as sensors of cations and anions. In this sense, the fluorescence emission, a property has proved very effective for this purpose. The series I ligands has two nitro groups per molecule, thereby quenching the fluorescence emission, so that the study could not be carried out on them. Instead, it was found effective as conveyor cations between two aqueous solutions through a membrane chloroform. Specifically, the ligand 2.2 'bis (1-aza-18-corona-6-carbonil) -4, 4'-dinitrobifenilo (10), was shown to have much affinity for Na + (greater than K + as has been waited a priori) and as a relevant fact, a large and anomalous transport of Li +, Cs +, Mg2 +, Ba2 +. The presence of two crowns in the same molecule, it creates a space hydrophilic inside the supramolecular complex that allows completely surround a cation too big for a single crown. In addition, 10 has proved to be a good switch redox able to take a Cd2 + and Zn2 + in its short form and assign the oxidized. The compounds of the series II and III does have a strong fluorescence. Thus have been characterized fotofísicamente, measured its quantum yield and the average life time. Their behavior has been studied in the presence of Zn2 +, Cd2 +, Cu2 +, Pb2 + and Ni2 +. There are many conclusions to be drawn from these studies. For example, the compound 2, 2'-bis (1-aza-18-corona-6-carbonil) -4.4 '- (dimethylamino) -bifenilo (11) experienced a marked softening of fluorescence in the presence of Zn2 + and not in the presence of Cd2 +. It is also capable of discriminating Zn2 + in the presence of Cd2 +, which makes you think of him as a good example of chemical sensor. These findings have been supported by a broad NMR study, which entails a lot of results that point in the same direction. The compound 2.2 'bis (1-aza-18-corona-6-metilen) -4.4' - (dimethylamino) -bifenilo (12) provides for an increase in fluorescence cations of alkali metals and alkaline, while their fluorescence is muffled in the presence of Zn2 + and Cd2 +. It has also studied the behavior of fluorescent compounds podandos. It has been found that this type of compound, the fluorescence is heavily influenced by the value of the angle dihedro between rings biphenyl. Thus, it is muffled if a link is established hydrogen intramolecular (between the carbonyl group in the series II and the 8 s groups 645 amino-chains, for example). The existence of such a bridge hydrogen has been confirmed experimentally because of the resolution by X-ray diffraction of a monocristal obtained with the compound 1 in the presence of HgI2. Although the compound 1 with nitro groups rather than dimethylamino, structural similarity with compounds podandos of Series II makes it possible to extrapolate this result. Finally, the compounds III series have been tested in the presence of anions (F-, Cl-, B-, HSO4-, H2PO3-, NO3). Contrary to what happens in the literature, in acid medium, in which the fluorescence of the compounds in the series III is muffled, an introduction of anions (mainly from fluoride anion), has the effect of the fluorescence and even recover often, the increase resulting in a fluorescence even higher than the initial amid neutral.

Author: TORTOSA MANZANARES MARIOLA.
Year: 2004.
University: AUTÓNOMA DE MADRID [www.uam.es].
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: INSTITUTO DE QUÍMICA ORGÁNICA . CONSEJO SUPERIOR DE INVESTIGACIONES CIENTÍFICAS.

Summary: Over the past two decades the use of sulfóxidos enantioméricamente cigars in asymmetric synthesis has experienced exponential growth, becoming the group sulfinilo one of the chiral auxiliary for more effective and versatile training stereocontrolada links CA and CX. Within the various types of compuestossulfinílicos, sulfóxidos, alfa-beta unsaturated constitute one of the groups most used in asymmetric synthesis. This thesis has been used as sulfóxidos chiral auxiliaries in various processes always follow a common goal: and [developing new methods for asymmetric synthesis for the participation of the group sulfinilo in subsequent transformations diastereoselectivas. In chapter 2 of the thesis describes in detail the transpositions of Claisen of sulfinil acrylates and other alil-sulfinil vinyl ethers. In the process are derived aldehydes and ketones, with one or two new chiral centers and also regenerates the unity of vinyl sulfoxide. In many cases sulfoxide allowed to carry out the reaction at temperatures not too high and in a relatively short time without using any kind of catalyst. It has been shown that in Z-sulfinil acrílatos the replacement C-5 is capable of reversing the course estereoquímico, forcing the replacement alilico to occupy a provision pseudoaxial in a state of transition type chair. Significantly, this investment is very rare and there are only two precedents in the literature. In chapter 3 has developed a method of synthesis enantioselectiva of hydroxy 2-sulfinil dienos from sulfinil c [orhidrinas. The combination of a metalación stereoselective led by the group sulfinilo followed by the elimination of oxirane without permits controlling the geometry of the new dual-link trisustituido in and [dieno generated. He then has been studied reactivídad Diels-Alder-hydroxy 2-and 3-sulfinil dienos revealing the sulfoxide controls in all cases selectivity -facial of cicloadición. With the introduction of replacement 2-metoxi-1-naftilo in sulfur have seen an increase in reactivity and selectivity in many of the examples studied. Finally in this chapter has described the first examples of Diels-Alder intrarTlOlecular of sulfinil dieninos. The presence of sulfoxide in dieno allowed to carry out the reaction with alquinos not activated under very mild, compared with the high temperatures required in similar systems without the group sulfinilo, which often limit its use in organic synthesis. The methodology developed allows obtaining carbo- and hetero, nitrogen and oxygen, 5 / 6 and 6 / 6 in condicioQes very soft, with good yields and days tereoselectividad is high. The final chapter has developed a new method of synthesis of dihidropiranos enantioméricamente cigars from hydroxy 3-sulfinil dienos. The process will generate 2 new chiral centers through a process ciclación intramolecular promoted by basis and directed by the group sulfinilo. The generality of the process has been demonstrated with changes in the geometry of dieno of departure as well as the degree of substitution was obtained in all cases excesses diastereoméricos high. This study has shown that from sulfinildihidropiranos through simple synthetic transformations can be accessed tetra and dihidropiranos differently funcionalizados, opening up possible routes to specific goals such as synthetics () -Disiherbaina.

Author: GARCIA CALVO NOELIA.
Year: 2004.
University: SALAMANCA [www.usal.es].
Place of defense: DEPARTAMENTO QUIMICA ORGANICA.
Place of preparation: DEPARTAMENTO QUIMICA ORGANICA.

Summary: In this report, from acid ent-halímico (component majority Halimium viscosum, Villarino of Aires), describes the synthesis of natural product chettaphanin I was performing a synthetic approach to triterpenes degraded skeleton picrasano and takes After the synthesis of diterpeno-alcaloide ent-agelasina C. The chettaphanin I is the first natural product of skeleton ent-halimano known, isolated from Adenochlaena siamensis, a plant used in traditional medicine. Structurally is a furanoditerpeno with several oxygen function which makes it very interesting from the point of view synthetic. Its synthesis has enabled corroborate its structure and establish its absolute configuration. The interest of quassinoides of skeleton picrasano is well known because of the wide range of biological activities offered. The synthetic approach made of these compounds, the system bicíclico acid ent-halímico is incorporated as part of a system BC tricyclic ABC. For the construction of a ring were considered two alternative routes, depending on the position C-3 nucleófila or electrófila. After a ciclación through condensation aldólica intramolecular, tricyclic system is achieved. In addition has opened a new avenue to reach in the future to the formation of the D ring obtained by both the ABCD system of picrasanos. Agelasina C epi-agelasina C are diterpeno-alcaloides of marine origin who have different biological activities: antimicrobials, enzyme inhibitors Na, K-ATPasa and antiadherentes. The synthesis of ent-agelasina C from acid ent-halímico and adenine has helped correct the structures proposed for these natural products. By comparing the physical and spectroscopic properties of the product of the synthesis of natural products, it has come to establish the structure and configuration absolute agelasina C which is enantiómera product synthesized in this work (ent-agelasina C), while for epi-agelasina C is proposed structure 17-epi-ent-agelasina C.

Author: FERNÁNDEZ FERNÁNDEZ ISABEL.
Year: 2004.
University: VIGO [www.uvigo.es].
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA UNIV. DE VIGO.

Summary: It conducts the study configuracional and conformacional of unity 5-metil-13-oxazolidi-2-ona. We optimized the sistesis of 5-iodometal-1, 3-oxazolidin-2-onas from amines alilicas, iodine and carbon dioxide. We studied the diastenselectividad of cidación in which it generates a new estenocentro using chiral auxiliaries. Prepare denados of oxazolidinomas with veriaciones on c-5 in the chain, finally preparing compounds enatiopuros. It was determined the absolute configuration of these compounds was established and its people conformecinal. It preperaron oligomers of methyl -1.3 - oxazolidin -2-ona by unions type of sequence homo-and hetero-quival with 2.3 and 4 units. We conducted the study using the same structural NMR, CD and molecular modeling. The results indicate the formation of hólice in homo-oligomeros obtained.

Author: FERNANDEZ MOLINA JORGE.
Year: 2004.
University: AUTÓNOMA DE MADRID [www.uam.es].
Place of defense: UNIVERSIDAD AUTONOMA DE MADRID.
Place of preparation: CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS (CSIC).

Summary: This thesis is divided into two chapters. The first part of the first chapter has explored the estereoquímica of adding intramolecular and intramolecular amine on 3-sulfonil dihidrofuranos, both for systems with a estereocentro additional position 5, as in systems disustituidos in that position. In the second part of the first chapter, from 3-sulfonil-2, 5-dihidrofuranos and through a series of chemical transformations have been validated different approaches toward obtaining 2-dimetilaminometil-4 ,5-diaril-2, 5 - dihidrofuranos, which could constitute a model for some products structurally similar to predict the effect of substitution on the antidepressant activity. The second chapter has undertaken the synthesis of (+) -goniofufurona and the (+) -7-epi-goniofufurona from hydroxy 3-sulfinil dienos. The synthetic sequence employed allows the generation of new analogues of these products in order to conduct a study structure. At present has been synthesizing and are being evaluated different analogues (+) -goniofufurona with different groups and aromatic heteroaromáticos at position 6. Initially, although the sequence could develop synthetic precursors optically pure, we decided to begin the study material racemate to simplify and lower the initial stages of the project. It was subsequently developed the method of synthesis of an advanced intermediate in the synthesis of (+) -goniofufurona in enantioméricamente pure from the D-xilosa easily and scale multigramo, which allowed us to continue with the synthetic material optically pure. The crux of the synthetic sequence is the opening of an epoxy sulfone and lactonización promoted by MgBr2. There are many examples of opening epoxy sulfones with different nucleotide to ketones substituted, both inter version as intramolecular However, as far as we know, is the first example of openness and lactonización by attack nucleófilo a carboxylic acids on an epoxy sulfones . Moreover, it has done the synthesis of a series of similar 7-deoxi of goniofufurona from a different approach, thus completing the synthetic sequence that began earlier in our working group. During the development of synthesis have been discovered new synthetic methods, as a new method for reducing opening epoxy sulfones using MgI2. Using this reagent is an alternative environmentally and economically preferable to the use of (PhSe) 2 and NaBH4. Moreover, the use of (PhSe) 2-NaBH4 can cause problems associated with the basic terms employed, while MgI2 is an effective way to carry out the opening-lowering epoxy sulfones in soft conditions. On the other hand, it has introduced a new method of synthesis of optically pure furans by ozonolisis of hydroxy 3-sulfinil dienos. This is an alternative method for the synthesis of sulfinil furans in the absence of strong basic conditions.

Author: DELGADO BLANCO F. JAVIER.
Year: 2004.
University: AUTÓNOMA DE MADRID [www.uam.es].
Place of defense: SALA DE GRADOS DEL EDIFICIO DE BIOLOGICAS.
Place of preparation: INSTITUTO DE QUIMICA ORGANICA GENERAL (C.S.I.C.).

Author: SIMON RUBIO LUIS MANUEL.
Year: 2004.
University: SALAMANCA [www.usal.es].
Place of defense: DEPARTAMENTO DE QUIMICA ORGANICA.
Place of preparation: DEPARTAMENTO DE QUIMICA ORGANICA.

Summary: The natural enzymes are best known catalysts. The aim of this thesis has been to design simple organic molecules that imitasen the behavior of enzymes, particularly for the addition of nucleotide neutral as thiol or unsaturated cyclic amines to carbonyls. The enzymes that catalyze reactions with accumulating burden in the states of transition is characterized, in general, by setting type polar interactions (eg hydrogen bond) to be strengthened as the reaction evolves into a state of transition. It is a very common type of structure called "anion hole" in which an atom acquires a partial negative burden in the state of transition is simultaneously forming two or more hydrogen bond with the active groups of the enzyme. The molecular receptors that we designed and synthesized in this dissertation is capable of simulating the behavior of such structures. During the argument demonstrated the need for recipients moléculares forming complexes with strong substrates of the reaction. For that reason was chosen as a lactam unsaturated substrate model that gave rise to complex stronger than could be obtained with other substrates such as lactones or ketones. As nucleotide model has been used pirrolidina and etilmercaptano. The pirrolidina be characterized as a strong link acceptor hydrogen, which can compete with the substrate in the reaction by preventing the formation of the complex with the receptor. It has studied the impact of the acidity giving link on the effect of hydrogen on the catalyst itself. The natural enzymes that have a "hole anionic" also have auxiliary groups which enhance the catalytic activity depends on the nature of which mechanism to catalyze the reaction. Studies have been conducted and kinetic theory about this mechanism, which has enabled conclude that the inclusion of amino groups, sulfones, and sulfonamide sulfóxidos could enhance the catalytic activity of the recipients. This has been confirmed after the preparation of molecular receptors that include these groups with a suitable geometry. It has been studied assistance chiral presenting some of these receptors which could synthesized enantioméricamente cigars or for which it could resolve the racemic mixture. This was necessary to develop a methodology based on the analysis of samples reaction by 1H-RMN after addiction of a desplazante chiral appropriate that has been designed and synthesized within this thesis. There have been proportions until 6 / 1 between the two enantiomers. In some cases, the results have been justified by conducting calculations modeling molécular using hybrids.