SYNTHESIS AND STRUCTURE OF NATURAL PRODUCTS

Author: RUIZ SUAREZ JUAN MANUEL.
Year: 2004.
University: LA LAGUNA.
Place of defense: INSTITUTO UNIVERSITARIO DE BIOORGANICA ANTONIO GONZALEZ.
Place of preparation: INSTITUTO UNIVERSITARIO DE BIOORGANICA ANTONIO GONZÁLEZ.

Summary: This thesis is divided into two parts, the first describes an approach to the synthesis Enantioselectiva of Decahidroquinolinas 2,5-disustitutidas (of toxins found naturally in exhudados skin of frogs from the family of Dendrobatidaes) based on the reaction of hetero Diels-Alder intramolecular. The second part focuses on a theoretical study, using the most powerful method at our disposal, the ab initio calculation of a series of processes conducted our research laboratory for those who needed some answers mecanísticas. These processes involving reactions hetero Diels-Alder between aldehydes and vinil-alenos; computationally studied the effect of different substitutions on the species vnilalénicas, hetero Diles-Alder intermolecular reactions between these species and aldehydes complexed with boron trifluoride, regrouping it was after a hetero Diels-Alder intermolecular reaction between vnil-alenos and benzaldehídos complexed with acid Lewis and the reactions of hetero Diels-Alder intramolecular of vinil-alenales.

Author: BRINKMANN YASMIN.
Year: 2004.
University: AUTÓNOMA DE MADRID.
Place of defense: UNIVERSIDAD AUTONOMA DE MADRID.
Place of preparation: UNIVERSIDAD AUTONOMA DE MADRID Y UNIVERSITE LOUIS PASTEUR DE ESTRASBURGO.

Summary: 1. Asymmetric Synthesis of fragment C32-C38 of Phorboxazoles. 2. Aproximacíon asymmetric with the synthesis of Hennoxazoles-Síntesis fragment C1-C12 of Hennoxazol D. 3. Survey methodology synthesis 1,3-dioles.

Author: MARJANET ARTIGAS GEORGINA.
Year: 2005.
University: AUTÓNOMA DE BARCELONA.
Place of defense: F.CIÈNCIES. DpTo..
Place of preparation: AUTÒNOMA DE BARCELONA.

Summary: The nature synthesizes a wide variety of molecules containing a ring of cyclohexane very funcionalizado with one or more establishments estereogénicos and who possess a wide range of biological activities. The project summary enantioselectiva of ciclohexanos polifuncionalizados using monoacetal enantiopuro of p-benzoquinona 10-feniltio-1 ,4-dioxaespiro [4.5] dec-6-en-8-ona, 1, as a substrate of departure have been synthesized a variety of key intermediates, both in racemic form as enantiopura, allowing us to address the various synthesis of natural products of biological interest. First has developed a summary of each of the enantiomers of trans-2-ciclohexen-1 ,4-diol. Its acquisition in our laboratories with a high excess enantiomérico and good performance is a new method of preparation of this compound. The gabosinas are a family of secondary metabolites structurally very interrelated that have been isolated from different strains of Sreptomyces. These compounds have a system metilciclohexano as skeleton carbonado guides and oxygen atoms as substituents. Among the biological activities described some gabosinas, as well as other related natural products are: effect of plant growth regulator, the anchoring properties of DNA, antibacterial activity, inhibition glicosidasas and glioxilasa-I (and therefore a potential anticancer action selective against certain tumors), activity antiprotozoica, etc.. Because of its unique structure and promising biological activity have been developed synthesis of some gabosinas, but the design of a comprehensive approach through a flexible synthetic methodology allowing access to as many as possible of these compounds from a common middle ground is still an unexplored . It has designed a synthetic approach to the family of gabosinas and other related compounds from a common intermediate, using a synthesis divergent from the same quirón 1. To avoid difficult chromatographic separations has developed a new methodology to get each of the enantiomers of the substrate of departure through a resolution químico-enzimática. The synthetic strategy has been applied for the preparation of (+) - and (-) - gabosinas N and O, and (+) - and (-) -epigabosinas N and O, which has been synthesized for the first time and, moreover, has been established absolute configuration of the gabosina Or natural 2R, 3R, 4R, 6S. Following this strategy in diversity have also been synthesized intermediates containing epoxide function, as well as others who have sustituyente hidroximetilo in position C6. Currently the research group is already working to complete the synthesis of other molecules goal from these key intermediates.

Author: Rustullet Oliver Albert.
Year: 2005.
University: AUTÓNOMA DE BARCELONA.
Place of defense: Facultad de Ciencias.
Place of preparation: Facultad de Ciencias. Universidad Autónoma de Barcelona.

Author: Mena Rejón Gonzalo.
Year: 2006.
University: LA LAGUNA.
Place of defense: Instituto Universitario Antonio González..
Place of preparation: Instituto Universitario de Bio-Orgánica Antonio González.

Summary: The search for natural bioactive molecules in recent years has been increasing in importance, debiado to the expansion of the human population and the resulting demand for food and habitat are advocating the extinction of numerous species of plants and animals, representing a loss irreparability of potential drugs, it is known that approximately 25% of the drugs used at present in industrialized countries originate or have been modeled from plant products. One of the most important sources in the search for bioactive molecules are plants that grow in tropical forests. Thus, Latin America is a treasure Depository pharmacist, and that approximately 60% of the plants of tropical forests are located from central Mexico to the central part of America SUr. In addition to this wealth, Latin America has a great diversity ethnobotany, based on the interaction of biological and cultural diversity, which is manifested in the widespread traditional use of plants for medicinal purposes by different ethnic Americans. This work is part of a project to study the medicinal flora American, which is aimed at finding new secondary metabolites in biological activity focused on species of the family Celastraceae. Investigations have been directed towards this family in particular, on the basis of background bibliographic describing products with cytotoxic activity, antimicrobial, antiviral, immunosuppressive, inhibits the activation of the Epstein-Barr virus, revertidora of multidrug resistance to drugs, antialimentaria and insecticide, other. The goals identified during the development of the work are described below: Revision of the taxonomic classification of the family Celastraceae. Literature review of diterpenos isolated celastráceas and their pharmacological activities. Aspects quimiotaxonómicos and etnofarmacológicos of genres Crossopetalum and Hippocratea. Isolation of secondary metabolites Crossopetalum gaumeri, Crossopetalum rhacoma and Hippocrateo exalted. Elucidación structural metabolites isolated with application of spectroscopic and spectrometric techniques. Study of the biological activities of secondary metabolites isolated: antimicrobial activity, antigiardiásica, cytotoxic and inhibits tumor promotion. Phytochemical contribution to the knowledge of the flora iberoamericana specifically of celastráceas of the Yucatan Peninsula. Study of the issues that may arise along research. Del worked for the realization of this report, but draw the following conclusions: * was achieved botanical collection and identification of three species celastráceas, from two subfamilies. Crossopetalum gaumeri and C. Rhacoma (Celastriodeae) and Hippocratea excelsa (Hippocrateideae). * From extract n-hexano/éter dietílico (1:1) from the bark of the root of C. Gaumeri was isolation and structural determination of 10 diterpenos and 9 triterpenoides, of which sesis proved to be new in literature chemistry (five diterpenos and triterpeno). * Diterpenos isolates of C. Gaumeri belong to the types podorcapano and abietatrieno. The abietatrienos known were: 12-hidroxi-8, 11, 13-abietatrieno (ferruginol) 12-hidroxi-8, 11, 13-abietatrien-7-ona (sugiol), 11, 12-dihidroxi-8, 11 , 13-abieta-trien-7-ona (demetilcriptojaponol) and 11, 12, 16-trihidroxi-8, 11, 13-abietatrien-7-ona (cyrtophyllona). The podocarpano was 12-hidroxi-13-metil-8, 11, 13-podocarpatrien-7-ona (nimbol). In both triterpenoides proved: pristimerina, 23-nor-6-oxo-pristimerol, 6-oxo-pristimerol, 7-hidroxi-6-oxo-pristimerol, blepharotriol, zeylasteral, isopristimerina III and 23-oxo-isopristimerina III. * The five diterp 8 enos nue f3b vos proved: 12-hidroxi-13-metil-5, 8, 11, 13-podocarpatetraen-7-ona (CGD-1), 5, 6-epoxi-12-hidroxi-13 - methyl-8, 11, 13-podocarpatrien-7-ona (CGD-2), 6B, 14-dihidroxi-8, 11, 13-abietatrieno (CGD-3), 12, 16-dihidroxi-8, 11, 13 - abietatrien-7-ona (CGD-4) and 11-hidroxi-8, 11, 13-abietatrien-16, 12-olida (CGD-5). Moreover, previously, methylester acid 6alfa, 10alfa-dihidroxi-2, 3-dioxo-24-nor-4, 7-friedoledien-29-oico and 5, 6-pristimerolida. * Four of the 11 diterpenos ailsaods proved to be new in the literature chemistry. They were: 5, 6alfa-epoxi-7beta, 12-dihidroxi-8, 11, 13-podocarpatrieno-13-carboxaldehido; 6alfa, 12, 13-trihidroxi-8, 11, 13-podocarpatrien-7-ona; 14-18beta - dihidroxi-8, 11, 13-abietatrieno and 13, 16-epoxi-maytenoquinona. * The species of the family of celastráceas not be characterized by producing diterpenos so that the isolation of 21 diterpenos the roots of C. Gaumeri and C. Rhacoma helps determine which species of the genus Crossopetalum are producing this kind of metabolites. * 13, 16-Epoximaytenoquinona can be considered as the second of its kind molecule isolated from a celastrácea over a period of 30 years. * The bis-diterpeno maytenona was isolated for the first time in 1961 and described on the basis of their thermal decomposition reactions, for that reason lacked data RMN-1H and 13C. This report provides the complete mapping of the signals, as well as the molecular structure obtained by X-ray diffraction * From extract n-hexano/diéter ethyl (1:1) from the bark of the root of Hippocratea excelsa were isolated three triterpenes, two triterpenoquinonas, trans-poliisopreno and dímero of triterpenoquinona. The 21alfa-hidroxiolean-12-en-3-ona and dimethyl ester acid 3,25-dinor-2 ,4-seco-4-seco-4-oxo-friedelano-1 ,5,7-trien-2, 29-dioecious. * It was possible to determine the antimicrobial activity, antigiardiásica front of Giardia intestinal cytotoxic and quimiopreventiva some of the molecules isolated. * It tested 17 compounds as against 13 strains of bacteria Gram positive and Gram negative. The compounds were tested nine diterpenos three triterpenes and five triterpenofenoles. The molecules of activity, compared with only did Gram positive bacteria. The diterpenos with hydroxyl groups in positions 11 or 14 were found to be active, indicating that these positions are essential for the activity. * Diterpenos CGD-2 and nimbiol were the most active compared to cell lines indicating that the presence of one or more epoxides in the molecule, as well as the presence of a ketone in position 7 is indicative of cytotoxic activity. * The diterpeno CGD-4 is considered promising as quimiopreventivo since the test in vitro inhibition generated close to 10% for the lowest concentration tested (10 mil / TPA) and the evidence "in vivo" fell over the third number papilomas in the 12-week period, reaching 1.6 papilomas / mouse at the end of the trial. * HET-1 and pristimerina were compounds that had activity against Giardia intestinalis and is the first occasion that are isolated triterpenes to this activity.

Author: Sánchez Izquierdo Francisco.
Year: 2006.
University: AUTÓNOMA DE BARCELONA.
Place of defense: Universidad Autónoma de Barcelona.
Place of preparation: Universidad Autónoma de Barcelona.

Summary: Excerpts from the roots and rhizomes of plants of the family Stemonaceae used for centuries in traditional medicines in Southeast Asian. These extracts are rich in compounds known as alkaloids Stemona. These alkaloids are composed polycyclic that are characterized by a structure in its nucleus of pirrolo [1,2-a] azepina or pirido [1,2-a] azepina. Moreover many of them have in their skeleton one or more rings alfa-metil-gamma-butirolactona. The work developed in this dissertation is part of one of the lines of research that our group is preparing diastereoselectiva of these alkaloids. This is used as a key step of the synthesis reaction of cicloadición 1,3-dipolar between a nitrona enantiopura acting as a source of quiralidad and a diester alpha beta-insaturado. This methodology has allowed us to prepare the alleged structure of the alkaloid isolated from natural sources known as Stemonidina and demonstrate that its allocation structural is wrong and that it's actually the alkaloid Stemospironina. Also in this thesis has been prepared lactone espiránica present at the alkaloid Stemospironina, which is expected to allow us to conclude its synthesis shortly.