ESTEREOCHEMISTRY AND CONFORMATIONAL ANALYSIS

Author: MAESTRE ASENJO ITZIAR.
Year: 2004.
University: AUTÓNOMA DE BARCELONA.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: ESCUELA DE POSTGRADO.

Summary: Within our research group have done many studies of the computational methods cyclodextrin, which are oligosaccharides cyclic alfa-D-glucopiranosa. The most common are those of 6, 7 and 8 glucose units (alpha, beta and gamma-ciclodextrian respectively). Taking into account the numeroros studies in recent years have arisen new avenues of investigation. This thesis has been studied first by DM methods in gas phase and aqueous solution the sciclodextrinas giants 14,21,26 and 28 glucoses and using different areas of strength (parm94, parm99 and glucam2000a and MM3 *) with the aim to find a model that will allow these systems correctly and be able to interpret the experimental data. In addition, to improve the characterization of these systems has been developed which allows a nomenclature to describe the relative position of monosaccharides into a chain of polysaccharides. It has come to the conclusion that the best force field is the glycam 2000th but in gas phase and in aqueous solution there are strong interactions soluto-disolvente. Besides the nomenclature developed has helped find specific sequences representing the shape of cyclodextrins. Moreover have studied the dimers of 3-O- (2-metilnaftil) -beta-ciclodextrinas, a ciclodextrian modified anchored groups. The authors of the synthesis of this modified cyclodextrin unable to identify what was the conformaicón this system but proposed three dimers two cabeza.cabeza (with a group anchored inside the cavity of the other cyclodextrin and the other groups anchored in parallel between the two cyclodextrins) and one cabeza-cola. Studies conducted by methods DM and GM have confirmed that certainly the dímero cabeza-cabeza with groups in the interior is the most stable entálpica and entropy. Lastly has opened a new avenue of inquiry in which systems are studied where cyclodextrins act as guests. We assessed the influence of a modified cyclodextrin (BCDm) in the degradation of a heat shock protein (Hsp) by the trypsin. Taking into account the experimental data, showing that BCDm inhibited in the presence of ATP hydrolysis, have proposed that the BCDm could form a complex partnership withthe Hsp or inhibit the activity of the ATP. The docking studies have shown that the first theory to be true given that the complex BCDm stands at the entrance to the crack of the Hsp, where the ATP, with the second theory tamibén could be true. Studies have remained at a preliminary stage and should continue to do a ranking of the complex as well as assessing the viability of the second theory proposed.

Author: CASAS ARCE EVA.
Year: 2004.
University: AUTÓNOMA DE BARCELONA.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: As a first objective of this dissertation addressed the synthesis enantioselectiva of nitronia 4, which would serve as the starting material for obtaining several alkaloids of groups Tuberostemospironina and Stemoamida. The strategy designed for the synthesis of this nitrona was to make a parimera reaction cicloadición 1,3-dipolar between nitrona aquiral 1 and alcohol alílico, controlling the course estereoquímico process through asymmetric catalysis, and a second oxidation reaction of cicloaductos obtained. Among Lewis acids tested, the combination of Et2Zn with EtZnCl has proven to be effective for the formation of the isoxazolidina trans-3. We have studied several dioles chiral symmetry C2, thereby in all cases a diastereoselectividad exo total. It is crucial to get the maximum number of points for coordination with the center zinca and, contrary to what might be expected a priori, it has induced greater enantioselectividad in the reaction has been the smaller size of diol, obtaining better results for the tartrate dimetilio front of other tartrates increased demand aesthetics. Finally, the introduction of iodine in the reaction medium has improved markedly over enantiomérico, up to 18%. Given that the best results in the reaction of cicloadición between nitrona 1 and alcohol alílico have led to an excess anantiomérico of 48%, oxidation adduct trans-3 lead to nitrona 4 with an excess enantiomérico moderate. As a second objective of this dissertation addressed the synthesis of alkaloid (-) -stenina, based on the nitrona 14, which has been synthesized by following the protocol described 1, wide multigramo. Advances in the synthesis of (-) -stenina from 14 are summarized in Scheme 2. It has reached the intermediate 44, which contains 3 of 4 rings in the alcoloide goal. From 44 have been synthesized several derivatives to test a reaction radicalaria of ciclación in order to close the last ring needed to complete the skeleton of (-) -stenina, but all attempts in this direction have proved fruitless. It has obtained valuable information on the reactivity of these intermediates, which should allow changes in the strategy for the successful completion of the synthesis of alkaloid.

Author: ANAKABE ITURRIAGA ENERITZ.
Year: 2004.
University: PAÍS VASCO.
Place of defense: FACULTAD DE CIENCIA Y TECNOLOGÍA.
Place of preparation: FACULTAD DE CIENCIA Y TECNOLOGÍA.

Summary: In this research have developed different methodologies sinéticas that allow access to different alkaloids isoquinolínicos. All of them have common employment b-aminoalcholes as a source of quiralidad acting as auxiliaries or as chiral blocks. Thus, the employment of (S, S )-(+)- pseudoephedrine as chiral auxiliary enables access arigglicinoles enantioméricamente enriched, precusores of 3-ariltetrahidroisoquinolinas through a synthetic methodology applicable to the synthesis estereocontrolada of such derivatives with a substitution at positions 7.8 in the aromatic core isoquinolínico. Moreover, the aminoalcohol, (S )-(+)- fenilglicinol, has been shown to be an efficient chiral building block for access to 1,2-diariletilaminas which, through ciclación lead to 3-ariltetrahidroisoquinolinas 6.7 - disustituidas optically active. The convenient manipulation of derivatives 3-ariltetrahidroisoquinolínicos synthesized has enabled obtaining a series of berbinas chiral among other R-tetrahidropalmatina, R-sinactina and (S) -xilopinina high excesses enantioméricos. Finally, it has made the total synthesis of alkaloid aporfinico natural (S) -glaucina used as a precursor chiral the aminoalcohol (S )-(+)- fenilglicinol which has assisted in obtaining (S) -laudanosina, which has been undertaken a process of oxidative coupling.

Author: FREIRE IRIBARNE FÉLIX.
Year: 2004.
University: SANTIAGO DE COMPOSTELA.
Place of defense: FACULTAD DE QUÍMICA.
Place of preparation: FACULTAD DE QUÍMICA.

Summary: In the introduction to this paper gives an overview on methods for allocating the absolute configuration of compounds monofuncionales by NMR and the problems that arise when extend this methodology to compounds polifuncionales, reviewed the limitations of these methods when apply to compounds polifuncionales. Also outlined in detail the various methods that exist so far to carry out the assignment of the absolute configuration of dioles either NMR or by or through Dicroísmo circular stressing the limitations presented. One of the conclusions to be drawn from this part of the tesis-es the lack of methods and reagents to carry out the assignment of the configuration dioles or trioles by NMR in a reliable manner. Therefore, the objectives of this thesis we are trying to assign the absolute configuration of díoles and trioles by NMR 1H. In order to do this work were used diolesy trioles configurations absolute known so that we know from a first principle the configurations of this type of compounds. As chiral auxiliaries were used AMAAs (MPA and 9-AMA). The methods we propose is based on esterificar the diol or triol with the two enantiomers from chiral auxiliary, recording NMR spectra and with the help of a model to allocate the absolute configuration of this type of compounds. To develop these models, have conducted a series of rigorous studies conformational based on circular dichroism studies, NMR studies at different temperatures, optimization calculations of structure, NMR calculations, analysis of the coupling constant, and study the effects apantallantes / desapantallantes produced by chiral auxiliary. This analysis has enabled us to generate a variety of methods to determine the absolute configuration of a series of compounds polifuncionales such as 1, n-dioles secondary / secondary 1,2-dioles chiral t minor, and 1,2,3 - trioles chiral in beta and gamma can be easily and reliably The study of such compounds, prompted us to do a review of the method of allocation of absolute configuration of chiral alcohols in primary, which enabled us to strengthen the method that had until the time to assign the absolute configuration of this type of compounds.

Author: BARNETO LOZANO JOSÉ LUIS.
Year: 2004.
University: EXTREMADURA.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: This paper studies the formation of amides simple theoretical and experimentally, suggesting behavior patterns useful in the structural analysis of large molecules like proteins. DFT B3LYP/6-31G * Calculations predict paralos isomers Z / E of secondary amides anti conformations between protons on the nitrogen and carbon alpha thereto (angle dihedron HNC alfa-H near 180Â °). They also predict a conformation in the rest acílico that isomers Z always puts a proton in anti oxygen carbonílico (angle dihedron OCC alfa-H near 180Â °). The interpretation of data from magnetic resonance imaging of acetamidas and formamidas secondary in relation to these conformational preferences has helped develop an equation, which describes the desapantallamiento caused by this method in connection with the geometric data, the protons CON-CH alpha. A similar study from the rest acílico made from carboxamidas has allowed propose another equation, which describes the desapantallamiento originated in the proton NCO-CH alpha. These equations have been used in the development of different expression, which enables the calculation of chemical displacement of the protons in proteins between two remnants peptídicos (-NH-CO-CHR-NH-CO-). In its application to the calculation of chemical movement in D2O of these protons in 2153 amino acids of 13 proteins, whose data are collected at banks structures, it has found an average error, or difference in absolute terms between the calculated displacement and found, 0.44 ppm, and a standard deviation of the average error of 0.35 ppm, statistics are indicative of the appropriateness of the methodology described.

Author: de Federico de la Rúa Miguel Álvaro.
Year: 2005.
University: AUTÓNOMA DE BARCELONA.
Place of defense: Facultad de Ciencias.
Place of preparation: Facultad de Ciencias.

Summary: In this thesis has been carried out through the study computational methods classics (AMBER) from three types of systems: a pseudorotaxano a catenane and a cyclodextrin perfluorometilada. In the first case has been studied pseudorotaxanos formed by a-ciclodextrina and each of the following molecules: acid 11-aminoundecanoico acid 12-aminododecanoico, 1,12-diaminododecano and acid 1,13-tridecanodioico. We have tried to estimate the continuing training [2] pseudorotaxano and [3] pseudorotaxano in aqueous phase for all systems through comparison of energy obtained from molecular dynamics. It also has tried to estimate the constant training for pseudorotaxano formed by the acid 11-aminoundecanoico and cyclodextrin through a calculating free energy FSL. In the second case has been studied a catenane consisting of (2, 6-di-O-metil) -b-ciclodextrina and a macrocycle which has two stations aromatic (a group bitolilo and other biphenyl-4, 4'-dicarbonilo) . It has been studied by favoring the cyclodextrin placed in a station or another by computation of free energy perturbation, and through integration termodiámica. It has been estimated that the cyclodextrin is located preferably on the station bitolilo with a weight of 88% of people on the other side. Finally, we have studied the difference in water solubility and complexing ability of the b-ciclodextrina perfluorometilada on b-ciclodextrina permetilada through calculations disruption of enrgía free. The reseultados have not been conclusive, but it has detected a fault high on the agenda RESP adjustment electrostatic charges.

Author: GARCIA FORTANET JORGE.
Year: 2005.
University: JAUME I DE CASTELLON.
Place of defense: ESC. SUP.DE TECN. Y CIENCIAS EXPERIMENTALES.
Place of preparation: ESC. SUP.DE TECN. Y CIENCIAS EXPERIMENTALES.

Summary: The objective of this Ph.D. Thesis is the synthesis of several natural lactones that can be classified into three groups, according to their ring size: small-sized (hyptolide, synargentolide A and passifloricin A), medium-sized (microcarpalide and lethaloxin) and large-sized (FD-891). Furthermore, gustastatin has been synthesized by means of photochemical esterification, showing the increasing utility of this new methodology developed by De Brabander and co. All the procedures have been carried out with high enantio and regioselectivities employing a wide range of the newest asymmetric methodologies. In this way, the main targets that have been achieved are: (a) the initial structure, elucidated by means of spectroscopic and physical data (hyptolide, microcarpalide, gustastatin and FD-891) has been checked; (b) the initial connectivity in synargentolide A has been proved to be wrong, and it has been corrected in the case of passifloricin A; (c) previous contradictions in lethaloxin have been clarified. At the same time, several non-natural isomers thereof have also been synthesized by means of minor modifications in the initial synthesis pathway. These non-natural derivatives may be potentially useful for structure-activity studies. These have already provided successfully results in some cases and areunder development in other ones.

Author: ESTIVILL DOMÉNECH CARLA.
Year: 2005.
University: AUTÓNOMA DE BARCELONA.
Place of defense: CENTRO NACIONAL DE MICROELECTRÓNICA.
Place of preparation: UNIVERSIDAD AUTÓNOMA DE BARCELONA.

Summary: The thesis is developed further studies on CSAs difuncionales. The first part describes the synthesis enantioselectiva by reducing stereoselective type CBS, the alpha alfa'-bis (trifluorometilo =- 9,10-antracendimentanamina, a CSA difuncional nature hidroxílica. Also conduct various studies by NMR, to understand the increased capacity enantiodiferenciadora regarding counterpart monofuncional. From the results we can attribute this phenomenon to the contribution in the states complexing of a partnership bidentada, where the substrate interacts with forces not enlazantes, with the two chiral centers of CFS. in the Part of the thesis design the stereoselective synthesis of CSAs type amine. The main objective was to synthesize the CSA difuncional alpha alfa'-bis (trifluorometilo) -9.10 -antracenodimetanamina, to be done through a trifluorometilación diastereoselectiva a sulfinimina chiral resulting from the condensation of 9,10-antracendialdehido with sulfinamida of Ellman. Later tests were conducted with a solvatación delos enantiomeros the new CSA.

Author: PÉREZ ROSA ESTHER M. SOLEDAD.
Year: 2005.
University: EXTREMADURA.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: This thesis describes the synthesis, structural and reactivity study of a wide variety of adducts from the condensation of aldehydes with 2-amino-2-dexoxialdosas (D-glucosamina, D-galactosa-mina, D-manosamina and 2-amino -2 - desoxi-D-glicero-L-gluco-heptopiranosa) and aminoalditoles (D-glucamina and N-metil-D-glucamina). It has been studied in detail the tautomería imina / enamina, balances anoméricos, balance ring piranosa / furanosa and conformational equilibrium, using techniques espectorscópicas, diffraction rayos-Xy calculations semiempíricos and ab initio and has identified a new effect estereolectrónico led by the pair of electrons group imine. It has perfected a simple synthesis N-acil and N-alquiloxazolidinas chiral from aminoalditoles and have prepared various aminoaldosas per-O-aciladas, which has been transformed into the corresponding isocyanates for reacicón with phosgene or trifosgeno. Finally, it has become these isocyanates react with mainoaldosas per-O-aciladas earlier generating miméticos of disaccharides to form a union of urea.

Author: ROYO GRACIA SOLEDAD.
Year: 2005.
University: ZARAGOZA.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: The work is part of the design of new amino acids and the study of its structural properties. In particular, it focuses on the study of different analogues phenylalanine, analyzing trends in a comprehensive conformational. Receive a different derivative of phenylalanine whose conformational preferences are known is very interesting, since the aromatic residues often play a key role in the processes of molecular recognition is often essential for a peptide receptor interacts with its biological. Specifically, it has carried out the synthesis of four derivative of phenylalanine in which exerts a greater or lesser degree of control over the orientation of its aromatic side chain. The selected are similar: difenilalanina (Dip), alfa-metildifenilalanina [(alfaMe) Dip], fluorenilglicina (Flg) and acid 1-N-terc-butoxicarbonilamino-c-2, t-3-difenil-1-ciclopropancarboxílico (c3diPhe ). All of them have been prepared both in form and in racemic form enantioméricamente pure developed for this new synthetic methodologies or implementing procedures described above. In all cases, the resolution of a synthetic intermediate by HPLC on chiral stationary phases allowed access to the corresponding amino acid in the form enantioméricamente pure and properly protected for use in peptide synthesis. The conformational preferences of these analogues phenylalanine have been identified by incorporating them into small peptides model and the structural study of the same has been done both in solution and in solid state through techniques such as nuclear magnetic resonance and infrared spectroscopy X-ray diffraction on monocrystals. These studies have identified how the modification in each derivative of phenylalanine affects their conformational preferences, correlating structure of the amino acid with the formation adopted by the peptide. Based on these results, one of the derivative of phenylalanine study has been selected for inclusion in a hormone peptide very interesting pharmacological bradykinin. The replacement of phenylalanine derivative modified by this has resulted in an increase in biological activity, demonstrating the interest analogues synthesized phenylalanine can have on the preparation of bioactive peptides with better pharmacological properties.

Author: PARRA RUIZ FRANCISCO JESÚS.
Year: 2005.
University: AUTÓNOMA DE MADRID.
Place of defense: FACULTAD DE CIENCIAS.
Place of preparation: FACULTAD DE CIENCIAS.

Summary: We have developed two new synthetic methods scalable industrial level for the synthesis of clarithromycin (6-O-metil erythromycin) from the pirimidiloxima erythromycin Woe to the tritil hidrazona erythromycin A. There have also been synthesized all products resulting from polimetilación in the macrocycle, as are the 6,11-O-dimetil eritomicia A, the 6,12-O-dimetil eritormicina A and 6,11,12-O-trimetil erythromycin A , compounds necessary for the quality control of the same. Finally, it has studied the origin of selectivity versus the methylation reaction of hydroxyl of macrocilo, analysis by X-ray, magnetic resonance imaging and molecular modeling.

Author: RUIZ CARRETERO PURIFICACION.
Year: 2006.
University: JAUME I DE CASTELLON.
Place of defense: E.S. DE TECNO. Y CIENCIAS EXPERI..
Place of preparation: ESCUELA SUPERIOR DE TECNOLOGIA Y CIENCIAS EXPERIMENTALES.

Summary: Because of that in literature there are few methods for the formation of aldoles configuration anti, we ask, in this thesis, a study of the additions aldólicas of enolatos ketones chiral polioxigenadas for the purpose of making aldoles with this configuration. This was used as a precursor of these ketones chiral the carbohydrate L-eritrulosa. The first objective was to prepare a ketone to submit the hydroxyl of estereocentro protected with a group electron attractive, and we had noticed that this factor allows us to obtain, in the process of enolización, enolatos configuration E, which when adicionaban to aldehydes were obtained with high estereocontrol, aldoles configuration anti. With the use of this ketone and a series of dehídos both aquirales as chiral were obtained such aldoles. Moreover, once certain conditions reaction there has been a conversion of these aldoles in a series of sintones d3 and d4 that serve as precursors to more complex molecules, ultimately, for the synthesis of natural products such as goniotalesdiol, goniofufurona and cardiobutanólido .