L'objectif de ce travail était d'accéder au squelette des alcaloïdes de type Aspidosperma et Strychnos à partir d'arylcyclohexa-2,5-diènes. Ces derniers sont d'abord synthétisés par réaction de Birch alkylante, puis ont été désymétrisés dans un premier temps par des réactions de Michael. Cette réaction fournit la cétone de Büchi, le noyau tétracyclique des alcaloïdes Aspidosperma en seulement en 6 étapes et un rendement global de 17%. Dans un second temps, la réaction d'amination oxydante catalysée par des métaux (Pd, Cu) a été développée. Cette réaction a permis un accès rapide au squelette pentacyclique d’aza-aspidospermanes et au squelette tétracycliques des alcaloïdes de type Strychnos. En parallèle, nous avons décrit une approche vers le squelette pentacyclique de la mossambine et la strychnine. / The aim of this work was to access the skeleton of the Aspidosperma and the Strychnos alkaloids using arylcyclohexa-2,5-dienes as common synthetic precursors. Initially, these arylcyclohexadienes were synthesized through Birch reductive alkylation reactions. The desymmetrization of these cyclohexadienes was developed via the Michael addition reaction, providing the Büchi ketone, the tetracyclic core of Aspidosperma alkaloids, in only 6 steps and 17% overall yield. On the other hand, we described the oxidative amination reaction catalyzed by metals (Pd, Cu). The palladium oxidative amination reaction allowed a fast access to the pentacyclic framework of aza-aspidospermanes and the tetracyclic framework of the strychnos. In parallel, we have described an approach toward the pentacyclic skeleton of mossambine and strychnine.

L’objectif de cette thèse était d’accéder au squelette de deux grandes familles d’alcaloïdes, les aspidosperma et les morphinanes, avec pour but, l’utilisation de précurseurs communs, les arylcyclohexa-2,5-diènes. Dans un premier temps, ces arylcyclohexa-2,5-diènes, obtenus par réaction de Birch alkylante, ont été désymétrisés par application de la réaction de Michael. Les substrats ainsi obtenus ont été diversement fonctionnalisés jusqu’à obtention du squelette pentacyclique des aspidosperma. Dans un second temps, plusieurs méthodologies utilisant des réactions de type Mannich ont été développées. Ces méthodologies ont permis d’atteindre une base tricyclique de la famille des morphinanes. Plusieurs transformations ont ensuite été examinées afin d’accéder au squelette tétracyclique avancé de cette famille d’alcaloïdes. / The objective of this work was to access the skeleton of two families of alkaloids, the aspidosperma and the morphinan, using arylcyclohexa-2,5-dienes as common synthetic precursors. In one hand, these arylcyclohexadienes, synthesized by reductive Birch alkylation, were desymmetrized via the Michael reaction. The resulting compounds were then functionalized to give the pentacyclic skeleton of aspidosperma alkaloids. On the other hand, several methodologies were developed using Mannich type reactions. These methodologies allowed an access to the tricyclic framework of the morphinan family. Several transformations were then examined to attain the tetracyclic skeleton of this family of alkaloids.

Ces travaux de thèse ont permis, au cours de deux projets, de s’attacher à la synthèse de structures complexes au moyen de réaction en cascade et de catalyse au rhodium.Dans une première partie, une méthodologie robuste pour la synthèse de 2,4,6-cycloheptatriénones entièrement substituées et non-symétriques par réaction de cycloaddition carbonylative [2+2+2+1] catalysée par des complexes de rhodium a été développée. Des mécanismes expliquant la formation des différents composés ont été proposés. Dans une seconde partie, l’application de l’hydroformylation désymétrisante catalysée au rhodium à la synthèse totale d’alcaloïdes indoliques de la famille Aspidosperma a été étudiée. Un intermédiaire clé de la synthèse de composés de type eburnane a ainsi été obtenu et sa transformation par différente stratégies été explorée. La synthèse totale de composés de type aspidosperma a été étudié, et les voies de synthèse explorées pourront être appliquées à des aldéhydes issus d’hydroformylation désymétrisante. / Through the course of two projects, this thesis work was concerned with the synthesis of complex scaffolds by means of cascade reactions and rhodium catalysis.In a first part, a new methodology was developed for the synthesis of non-symmetrical and fully substituted 2,4,6-cycloheptatrienones by rhodium-catalysed [2+2+2+1] carbonylative cycloaddition. Mechanisms for the formations of the observed compounds were proposed.In a second part, the application of rhodium-catalysed desymmetrising hydroformylation to the total synthesis of Aspidosperma indole alkaloids was studied. A key intermediate in the synthesis of eburnan-type alkaloids was thus obtained, and its transformation into th desired compounds using various strategies was explored. The total synthesis of aspidosperma-type alkaloids was studied, and the explored syntheses will be applied to aldehydes obtained by desymmetrising hydroformylation.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Este trabalho relata o estudo fitoquÃmico das sementes de Aspidosperma pyrifolium (Apocinaceae), descrevendo o isolamento e a determinaÃÃo estrutural de um alcaloide inÃdito com esqueleto plumerano rearranjado, o (-)-(3S,7S,21R)-rel-(3αH)-15(14→3)-abeo-2,16,17,20,6,7-hexahidro-15H,8aH,16a,20a-etano-1H-indolizino[3,1-cd]carbazol, alÃm de onze compostos conhecidos, seis alcaloides plumeranos identificados como aspidospermina, desmetoxiaspidospermina, pirifolina, 15-desmetoxipirifolina, aspidofractinina e N-acetilaspidofractinina; um alcaloide tetra-hidro-β-carbolÃnico, a N-metilacuamidina; dois iridoides glicosilados, Ãcido logÃnico e loganina; um derivado do Ãcido salicÃlico, o Ãcido 2-hidrÃxi-3-O-β-D-glicopiranosilbenzÃico; e um derivado metilado do inositol, o 2-O-metil-L-quiro-inositol. Os compostos foram isolados por tÃcnicas cromatogrÃficas, principalmente a Cromatografia LÃquida de Alta EficiÃncia, e suas estruturas foram determinadas atravÃs de anÃlises por RMN, uni e bidimensionais, IV e EMAR, alÃm da comparaÃÃo com dados da literatura. Apesar de jà descritos na literatura, cinco compostos sÃo relatados pela primeira vez para a espÃcie, e um està sendo relatado pela primeira vez como produto natural, de origem vegetal. A revisÃo dos dados de RMN da literatura de alguns alcaloides isolados, e as correspondentes correlaÃÃes estruturais, juntamente com um levantamento bibliogrÃfico (de 1973 a 2013) dos dados de RMN 13C de alcaloides plumeranos isolados da famÃlia Apocinaceae, tambÃm sÃo descritos neste trabalho. A fraÃÃo aquosa resultante da partiÃÃo lÃquido-lÃquido do extrato etanÃlico das sementes de A. pyrifolium, fonte da maioria dos compostos isolados, apresentou atividades antinociceptiva e anti-inflamatÃria nos testes de formalina, contorÃÃo abdominal induzida pelo Ãcido acÃtico e edema de pata por carragenina. / This work reports the phytochemical analysis from seeds of Aspidosperma pyrifolium (Apocynaceae), describing the isolation and the structural characterization of a unknown alkaloid with a rearranged plumeran skeleton, the (-)-(3S,7S,21R)-rel-(3αH)-15(14→3)-abeo-2,16,17,20,6,7-hexahydro-15H,8aH,16a,20a-ethano-1H-indolizino[3,1-cd]carbazole, in addition to eleven known compounds, six plumeran alkaloids identified as aspidospermine, demethoxyaspidospermine, pirifoline, 15-demethoxypirifoline, aspidofractinine and N-acetylaspidofractinine; a tetrahydro-β-carboline alkaloid, the N-methylakuammidine; the glycosides of two iridoids, loganic acid and loganin; a salycilic acid derivative, 2-hydroxy-3-O--D-glucopyranosylbenzoic acid; and a methyl inositol derivative, the 2-O-methyl-L-chiro-inositol. The compounds were isolated by chromatographic techniques, especially High Performance Liquid Chromatography, and their structures were characterized by 1D and 2D NMR spectroscopy, FT-IR and HRESIMS, and comparison with data from literature. Altough already reported in the literature, five compounds are being reported for the first time for the species, and one is being reported from a natural source. The NMR data, and the correspondent assignments of some alkaloids already reported in the literature, together with a bibliographic survey (from 1973-2013) of the 13C NMR data of plumeran alkaloids isolated from the Apocynaceae family, are presented in this work. The residual aqueous fraction of the liquid-liquid partition of the ethanol extract from seeds of A. pyrifolium, source of most compounds isolated, showed antinociceptive and anti-inflammatory activities in the formalin test, abdominal writhing induced by acetic acid, and paw edema induced by carrageenan.

Understanding of the diverse aspects affecting the regeneration ecology of species is crucial to make decisions regarding management and conservation strategies, especially in highly fragile and threatened ecosystem as the Neotropical savanna (cerrado) formations. Available knowledge of regeneration ecology of cerrado species is too limited to attain optimal or suitable management actions. The objectives of the present study were: i) analysis of the characteristic parameters of the anemochorous seed dispersal of study species Q. grandiflora, (ii) determine the spatial distribution of tree species Q. grandiflora for growth stages (seedlings to juveniles) and interrelations between the stages, and (iii) determining variables of the spatial distribution of recruitment of tree species A. tomentosum. The present study was conducted in the cerrado Aguara Ñu of the Mbaracayú Nature Forest Reserve located in the northeast of Paraguay. The cerrado Aguara Ñu is part of the Mbaracayú Biosphere Reserve and represents one of the most important ecoregions in the world, the cerrado ecosystem. The cerrado biome encompasses areas from northeastern to southwestern Brazil, eastern Bolivia, and northern Paraguay. It is characterized by the presence of high plant and animal biodiversity and also high endemism (Myers et al., 2000). Tree species Q. grandiflora and A. tomentosum are typical species of the cerrado formation. Based on the selected investigated regeneration cycle stages of study tree species Q. grandiflora and A. tomentosum, the present thesis describes the spatial analysis of recruitment of both study species and the anemochorous diaspore dispersal of tree species Q. grandiflora. The purpose of the present investigation is to address regeneration aspects not attained so far as certain seed dispersal aspects, such as seed densities and distances from conspecific adult trees and spatial arrangements of seedlings of species A. tomentosum. Results of the present study aim to contribute to existing information and at the same time provide new knowledge on ecological aspects so far not investigated. Research results on seed dispersal of tree species Q. grandiflora revealed that dispersal can be modeled by inverse modelling considering isotropy and lognormal density function presenting mean dispersal distances of 10.69 to 62.48 m. Estimations of the fruit production of a seed tree yielded a total 50671 to 70632 (DBH = 70 cm). Results of spatial arrangement of seedlings and juveniles revealed a significant distance effect to conspecific adult trees. Moreover, results also showed: (i) highest densities or intensities (m2) of seedlings (heights <50 cm) close to the conspecific adult trees and (ii) a shift of intensity of seedlings with increase of growth stage or size for tree species Q. grandiflora. Additionally, seedlings (up to 200 cm height) of study species Q. grandiflora indicated gradual decreasing clumping patterns and juveniles (200 – 500 cm height) presented clumping patterns. Modelling results of spatial patterns of seedlings (heights ≤ 200 cm) of study tree species A. tomentosum revealed aggregation patterns. Moreover, shade effect resulted to be a statistical significant factor for the establishment of seedlings of tree species A. tomentosum (p-value = 0.0266), whereas distance effect to seed tree resulted not significant (p-value= 0.4936). Considering the findings of seed dispersal and spatial patterns analysis of tree species Q. grandiflora and A. tomentosum some management aspects to be attained for conservation purposes are avoiding fragmentation of the ecosystem, management of the spatial and time fire frequency and maintain minimum amount of seed trees per unit area in order to guarantee successful recruitment.:1. Introduction 1 References 8 2. Materials and Methods 13 2.1 Characterization of the cerrado biome 13 2.2 Description of the study area and study sites 15 2.3 Characterization of the study tree species 23 2.3.1 Qualea grandiflora (Mart.) 23 2.3.2 Aspidosperma tomentosum (Mart.) 24 2.4 Principles and selection criteria 25 2.5 Data collection 26 2.5.1 Seed dispersal 26 2.5.2 Spatial patterns of plants 27 2.6 Data analysis 28 2.6.1 Statistical analysis of data 28 2.6.2 General statistical procedures of data analysis 30 2.6.3 Spatial point process analysis – Inverse modelling and spatial point patterns 31 2.6.4 Spatial point patterns analysis procedure 33 2.6.4.1 Descriptive statistics in spatial point patterns 36 2.6.4.1.1 Distance effect of seedlings from seed trees (rhohat function) 36 2.6.4.1.2 Pair correlation function (pcf) 36 2.6.4.2 Point process modelling 38 References 43 3. Seed dispersal of Qualea grandiflora (Mart.) 49 3.1 Introduction 49 3.2 Methodology 51 3.2.1 Data collection and seed trap design 51 3.2.1 Data analysis – inverse modelling 53 3.3 Results 58 3.3.1 Seed density 58 3.3.2 Inverse modelling results – seed production, dispersal and distances 60 3.3.2.1 Isotropic modelling 61 3.3.2.2 Anisotropic modelling 63 3.3.2.3 Statistical comparison isotropy vs. anisotropy 66 3.4 Discussion 67 3.4.1 Applied methodology for seed dispersal – trap design and inverse modelling 67 3.4.2 Seed dispersal modelling 69 3.5 Conclusion 74 References 75 4. Spatial analysis of Qualea grandiflora (Mart.) 80 4.1 Introduction 80 4.2 Methodology 82 4.2.1 Data collection – Field sampling 82 4.2.2 Data analysis 85 4.2.2.1 Spatial point pattern – Explorative analysis 85 4.2.2.2 Point process modelling (Poisson and Gibbs models) 87 4.2.3 Results 89 4.2.3.1 Spatial distribution of individuals of study species 89 4.2.3.2 Modelling distance effect of recruitment to adult trees 95 4.2.4 Discussion 102 4.2.4.1 Applied methodology for spatial analysis of study species 102 4.2.4.2 Spatial arrangement of study species 103 4.2.5 Conclusion 109 References 109 5. Spatial analysis of Aspidosperma tomentosum (Mart.)115 5.1 Introduction 115 5.2 Methodology 117 5.2.1 Data collection – Field sampling 117 5.2.2 Data analysis 120 5.2.2.1 Spatial point pattern – Explorative analysis 120 5.2.2.2 Point process modelling – Replicated point patterns 120 5.3 Results 123 5.3.1 Spatial distribution of natural regeneration of study species 123 5.3.2 Modelling shade and distance to seed tree effect on natural regeneration of study species 130 5.4 Discussion 133 5.4.1 Applied methodology for data collection and analysis 133 5.4.2 Spatial distribution of natural regeneration of study species 134 5.5 Conclusion 139 References 140 5. Concluding discussion and summary 146 6.1 Regeneration ecology of Qualea grandiflora and Aspidosperma tomentosum 146 6.1.1 Inferences on relation of seed dispersal and spatial distribution of recruitment of Qualea grandiflora 146 6.1.2 Inferences on spatial patterns of recruitment of Aspidoserma tomentosum 149 6.2 Management implications for Qualea grandiflora Aspidosperma tomentosum 150 6.3 Future research 153 6.4 Concluding summary 154 References 155

All Strychnos and Aspidosperma alkaloids possess a core pyrrolo[2,3-d]carbazole ABCE tetracycle. In order to develop an efficient and divergent methodology for the synthesis of Strychnos alkaloids, a streamlined synthetic sequence to the ABCE tetracycle has been developed. It features a Mitsunobu activation of an N-hydroxyethyl gramine intermediate and subsequent intramolecular aza-Baylis-Hillman reaction. This method was first applied in the total synthesis of (±)-alstolucine B. Additional key steps in the synthesis included (1) chemoselective intermolecular and intramolecular Michael additions and (2) a Swern indoline oxidation. The second application of this method was in the first total synthesis of (-)-melotenine A, a novel rearranged Aspidosperma alkaloid with potent biological activity. Additional key steps in the synthesis included (1) a Piers annulation of a vinyl iodide and a methyl ketone to prepare the D ring and (2) a site-selective intermolecular vinylogous aldol reaction / Chemistry

Thesis advisor: Amir H. Hoveyda / Chapter 1: Efficient Z-Selective Cross-Metathesis of Secondary Allylic Ethers Efficient Z-selective cross-metathesis of secondary allylic ethers were catalyzed by monoaryloxide monopyrrolide molybdenum complexes. Reactions involving both silyl and benzyl protected ethers were demonstrated, as well as ethers containing alkyl, aryl and alkynyl substituents. Mechanistic studies were performed, and the reactions were applied to the total synthesis of several ene-diyne natural products. Chapter 2. Stereoselective Total Synthesis of Disorazole C1 The stereoselective total synthesis of disorazole C1 is reported. The synthesis was completed in 12 longest linear steps. Our synthesis demonstrates the utility of Z-selective cross-metathesis to form both alkenyl borons and alkenyl halides. Another key transformation was a one-pot Suzuki-dimerization reaction to form a symmetric 30 membered ring in relatively high yield. Chapter 3. Stereoselective Cross-Metathesis to Form Trisubstituted Alkenes Initial studies into the stereoselective formation of trisubstituted olefins through molybdenum catalyzed cross-metathesis have been performed. Our mechanistic understanding of the reaction lead us to focus on the synthesis of alkenyl halides, which can be obtained in up 90% yield and 75:25 E:Z selectivity. Chapter 4: Ring-Closing Metathesis in the Synthesis of Natural Products Development of highly efficient and selective ring-closing metathesis reactions have enabled collaborators to successfully implement routes in total synthesis endeavors. A diastereoselective seven-membered ring-closing metathesis enabled the successful synthesis of (±)-tetrapetalone A methyl-aglycon. An enantioselective ring-closing metathesis to form a six membered ring has provided access to enantioenriched aspidosperma alkaloids. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-03-22T19:30:53Z No. of bitstreams: 1 MairaConceicaoJeronimoDeSouzaLima_TESE.pdf: 6599799 bytes, checksum: 12ec2e74167618ab1f1b22a3284a60a5 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-03-23T23:43:41Z (GMT) No. of bitstreams: 1 MairaConceicaoJeronimoDeSouzaLima_TESE.pdf: 6599799 bytes, checksum: 12ec2e74167618ab1f1b22a3284a60a5 (MD5) / Made available in DSpace on 2016-03-23T23:43:41Z (GMT). No. of bitstreams: 1 MairaConceicaoJeronimoDeSouzaLima_TESE.pdf: 6599799 bytes, checksum: 12ec2e74167618ab1f1b22a3284a60a5 (MD5) Previous issue date: 2015-04-17 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / Envenenamentos causados por animais pe?onhentos s?o um grave problema de sa?de p?blica, enquadrando-se nesse cen?rio, principalmente, os escorpi?es e as serpentes. Tityus serrulatus ? considerado o escorpi?o mais venenoso da America do Sul, devido ? alta toxicidade do seu veneno, respons?vel por causar acidentes graves, principalmente em crian?as. A esp?cie Bothrops jararaca ? uma serpente que possui no seu veneno uma mistura complexa de enzimas, pept?deos e outras mol?culas. As toxinas do veneno de B. jararaca induzem respostas inflamat?rias locais e sist?micas. O tratamento de escolha para os casos graves de envenenamento ? a administra??o intravenosa do antiveneno especifico. Por?m, nem sempre esse tratamento est? acess?vel para os moradores de zonas rurais, que fazem uso de extratos de plantas medicinais. Nesse contexto, extratos aquosos, fra??es e compostos isolados de Aspidosperma pyrifolium (pereiro) e Ipomoea asarifolia (salsa), usadas na medicina popular, foram objeto de estudo deste trabalho para avaliar a atividade anti-inflamat?ria nos modelos de peritonite induzida por carragenina e peritonite induzida pelo veneno de T. serrulatus (VTs), e nos no modelo de edema local e infiltrado inflamat?rio induzido pelo veneno de B. jararaca, administrados pela via intravenosa. Os resultados dos ensaios de citotoxidade utilizando o ensaio MTT demonstraram que os extratos aquosos das esp?cies vegetais apresentaram baixa toxicidade para c?lulas provenientes de fibroblasto de embri?o de camundongo (3T3). A an?lise qu?mica dos extratos por Cromatografia L?quida de Alta Efici?ncia revelou a presen?a do flavon?ide rutina, na A. pyrifolium, e rutina, ?cido clorog?nico e ?cido caf?ico, na I. asarifolia. Quanto ? avalia??o farmacol?gica, os resultados demonstraram que o pr?-tratamento com extratos aquosos e fra??es reduziram a migra??o de leuc?citos totais para a cavidade abdominal no modelo de peritonite causada por carragenina e no modelo de peritonite induzida por veneno de T. serrulatus. Ainda, esses grupos apresentaram atividade antiedematog?nica, no modelo de edema local causado pelo veneno de B. jararaca, e reduziram o infiltrado inflamat?rio para o m?sculo. Os soros (antiaracn?dico e anti-botr?pico) espec?ficos para cada veneno atuaram inibindo a a??o inflamat?ria dos venenos e foram utilizados como controles. Os compostos identificados nos extratos, rutina, ?cido clorog?nico e ?cido caf?ico, tamb?m foram testados e, assim como os extratos das plantas, exibiram efeitos anti-inflamat?rios significativos, nas doses testadas. Dessa forma, esses resultados d?o evid?ncias, ?s plantas estudadas, de potencial atividade anti-inflamat?ria. Esse ? o primeiro estudo que avaliou os poss?veis efeitos terap?uticos de A. pyrifolium e I. asarifolia, mostrando o potencial terap?utico que essas esp?cies possuem. / Envenomation caused by venomous animals, mainly scorpions and snakes, are a serious matter of public health. Tityus serrulatus is considered the most venomous scorpion in South America because of the high level of toxicity of its venom. It is responsible for causing serious accidents, mainly with kids. The species Bothrops jararaca is a serpent that has in its venom a complex mixture of enzyme, peptides and other molecules. The toxins of the venom of B. jararaca induce local and systemic inflammatory responses. The treatment chosen to serious cases of envenomation is the intravenous administration of the specific antivenom. However, the treatment is not always accessible to those residents in rural areas, so that they use medicinal plant extracts as the treatment. In this context, aqueous extracts, fractions and isolated compounds of Aspidosperma pyrifolium (pereiro) and Ipomoea asarifolia (salsa, salsa-brava), used in popular medicine, were studied in this research to evaluate the anti-inflammatory activity in the peritonitis models induced by carrageenan and peritonitis induced by the venom of the T. serrulatus (VTs), and in the local oedema model and inflammatory infiltrate induced by the venom of the B. jararaca, administrated intravenously. The results of the assays of cytotoxicity, using the MTT, showed that the aqueous extracts from the plant species presented low toxicity to the cells that came from the fibroblast of the mouse embryo (3T3).The chemical analysis of the extracts by High Performance Liquid Chromatography revealed the presence of the rutin flavonoid, in A. pyrifoliu, and rutin, clorogenic acid and caffeic acid, in I. asarifolia. Concerning the pharmacological evaluation, the results showed that the pre-treatment using aqueous extracts and fractions reduced the total leukocyte migration to the abdominal cavity in the peritonitis model caused by the carrageenan and in the peritonitis model induced by the T. serulatus venom. Yet, these groups presented anti-oedematous activity, in the local oedema model caused by the venom of the B. jararaca, and reduced the inflammatory infiltrate to the muscle. The serum (anti-arachnid and anti-bothropic) specific to each venom acted inhibiting the inflammatory action of the venoms and were used as control. The compounds identified in the extracts were also tested and, similar to the plant extracts, showed meaningful anti-inflammatory effects, in the tested doses. Thus, these results are indicating the potential anti-inflammatory activity of the plants studied. This is the first research that evaluated the possible biological effects of the A. pyrifolium and I. asarifolia, showing the biological potential that these species have.

Submitted by Jean Medeiros (jeanletras@uepb.edu.br) on 2017-11-22T15:06:31Z No. of bitstreams: 1 PDF - Francisca Sabrina Vieira Lins.pdf: 35801334 bytes, checksum: 8059ebb90dfd1f13c725078faab4deca (MD5) / Approved for entry into archive by Secta BC (secta.csu.bc@uepb.edu.br) on 2017-12-06T18:44:30Z (GMT) No. of bitstreams: 1 PDF - Francisca Sabrina Vieira Lins.pdf: 35801334 bytes, checksum: 8059ebb90dfd1f13c725078faab4deca (MD5) / Made available in DSpace on 2017-12-06T18:44:30Z (GMT). No. of bitstreams: 1 PDF - Francisca Sabrina Vieira Lins.pdf: 35801334 bytes, checksum: 8059ebb90dfd1f13c725078faab4deca (MD5) Previous issue date: 2016-08-31 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Aspidosperma pyrifolium Mart. Apocynaceae is a family plan, known as pereiro, stick pereiro, pereiro-red, stick-to-coaru. It has wide spread throughout the area of savanna and in traditional medicine is used to treat respiratory disorders and fever. The study aimed to carry out the isolation and identification of the chemical constituents of hexâncica phase and the fraction of total alkaloids (FAT-Ap) (from the ethanol extract of the stem bark) by chromatographic and spectroscopic techniques (infrared spectroscopy and spectroscopic Nuclear Magnetic resonance of) and pharmacological tests (by inflammation and analgesic models) and acute toxicity, the fraction of total alkaloids (FAT-Ap). Thus, were isolated for the first time in Aspidosperma Genro, the paristina compounds (anthraquinone) and liquexantona (xanthone), the hexane phase. Also they were isolated for the first time in this species the triterpenes lupeol and β - amyrin, removed the hexane phase. Although the phytochemical study, the FAT -Ap was subjected to high-performance liquid chromatography, which allowed the isolation and identification of two indole alkaloids monoterpenoid of plumerano core (15 metoxipirifolidina and 15 metoxiaspidospermina. To evaluate the anti-inflammatory potential were performed paw edema test and test peritonitis, both induced by carrageenan. As for evaluating the anti - nociceptive activity was chosen for nociception models of formalin induced writhing test induced by acetic acid. As for the pharmacological results, the FAT-Ap showed anti- inflammatory potential both as analgesic, reaching up to 85.57% inhibition (at 30 mg / kg) of writhes induced by acetic acid, versus animal models. Thus, this kind has proved promising source of substances with therapeutic potential. However, care is presented for the reservation - toxicity (LD50 = 160 mg / kg), thus conditioning its use for the determination of safe doses. / Aspidosperma pyrifolium Mart. é uma planta da família Apocynaceae, conhecida como pereiro, pau-pereiro, pereiro-vermelho, pau-de-coaru. Tem larga dispersão em toda a zona da caatinga e na medicina tradicional é utilizada no tratamento de distúrbios respiratórios e febre. O estudo teve como objetivo realizar o isolamento e a identificação dos constituintes químicos da fase hexâncica e da fração de alcaloides totais (FAT-Ap) (provenientes do extrato etanólico bruto das cascas do caule) por técnicas cromatográficas e espectroscópicas (espectroscopia no Infravermelho e espectroscopia de Resonância Magnética Nuclear) bem como testes farmacológicos (através de modelos de inflamação e analgesia) e de toxicidade aguda, da fração de alcaloides totais (FAT-Ap). Desta forma, foram isolados pela primeira vez no gênro Aspidosperma, os compostos paristina (antraquinona) e liquexantona (xantona), da fase hexânica. Foram isolados também pela primeira vez nesta espécie os triterpenos lupeol e β-amirina, retirados da fase hexânica. Ainda no estudo fitoquímico, a FAT-Ap foi submetida à cromatografia líquida de alta eficiência, o que permitiu o isolamento e identificação de dois alcaloides indólicos monoterpenoides de núcleo plumerano (15–metoxipirifolidina e 15- metoxiaspidospermina. Para avaliar o potencial anti-inflamatório foram realizados teste de edema de pata e teste de peritonite, ambos induzidos por carragenina. Já para avaliar a atividade anti-nociceptiva optou-se pelos modelos de nocicepção induzida por formalina e teste de contorções abdominais induzida por ácido acético. Quanto aos resultados farmacológicos, a FAT-Ap apresentou potencial tanto anti-inflamatório quanto analgésico, atingindo até 85,57% de inibição (na dose de 30 mg/kg) das contorções induzidas por ácido acético, frente aos modelos animais. Deste modo, tal espécie mostrou-se fonte promissora de substâncias com potencial terapêutico. Todavia, ressalva-se o cuidado para a toxicidade apresentada (DL50 =160 mg/kg), sendo assim seu uso condicionado à determinação de doses seguras.

Submitted by (edna.saturno@ufrpe.br) on 2016-10-13T13:29:39Z No. of bitstreams: 1 Jose de Castro Souza Neto Junior.pdf: 703541 bytes, checksum: 3ed13bbfae81442d4bddd813c36f8ade (MD5) / Made available in DSpace on 2016-10-13T13:29:39Z (GMT). No. of bitstreams: 1 Jose de Castro Souza Neto Junior.pdf: 703541 bytes, checksum: 3ed13bbfae81442d4bddd813c36f8ade (MD5) Previous issue date: 2012-02-13 / The ingestion of toxic plants is an important cause of problems related to health status of herds cattle, goat and sheep, affecting different areas of animal health, one of the playback. Many plants are capable, when ingested to cause diseases in ruminants, affecting many different organs and systems, including the reproductive system. This experiment aimed to evaluate the ability to change reproductive crude extract alkaloids of Aspidosperma pyrifolium in pregnant wistar rats. We used 18 pregnant rats were divided into three experimental groups of 06 animals each, according to treatment received by gavage from the first until the twentieth day of pregnancy, namely: Group I (EP) - treated animals with the placebo extract (01 ml of water / day); Group II (ECA1) – treated animals with concentrated extract alkaloids of Aspidospema pirifolium at a concentration of 0.002 mg / ml; Group III (ACE2) - treated animals with concentrated extract alkaloids of Aspidospema pirifolium at a concentration of 0.004 mg / ml. Significant increase in weight in the animals of group (I) and a relative increase in the animals of group (II), whereas the amines of the group (III) showed no significant change in weight during pregnancy. At 20 days of pregnancy on the number of fetuses, were observed the following results: Group I: average of 4.33 fetuses / female: Group II: average of 1.33 fetuses / female and Group III: average of 0.00 fetuses / female (females without fetuses). It is concluded that the concentrated extract alkaloids of Aspidospema pirifolium modifying reproduction of rats when administered from 1st to 20th day of pregnancy, causing weight loss in rats and decrease the number of fetuses (concentration 0.002 mg / ml) and weight loss and absence of fetuses (concentration 0.004 mg / ml). / A ingestão de plantas tóxicas representa uma importante causa de problemas relacionados ao estado sanitário de rebanhos bovino, caprino e ovino, afetando diferentes áreas da saúde animal, sendo uma delas a reprodução. Várias plantas são capazes, quando ingeridas, de causar dano à saúde dos ruminantes, afetando os mais diferentes órgãos ou sistemas, inclusive o reprodutivo. Este experimento teve o objetivo de avaliar a capacidade de alteração reprodutiva do extrato bruto alcaloídico de Aspidosperma pyrifolium em ratas wistar prenhes. Para isto foram utilizadas 18 ratas prenhes divididas em três grupos experimentais de 06 animais, conforme tratamento recebido por via endoesofágica do primeiro ao vigésimo dia de prenhez, a saber: Grupo I (EP) - animais tratados com Extrato Placebo (01 ml de água/dia); Grupo II (ECA1) - animais tratados com Extrato Concentrado Alcaloídico de Aspidospema pirifolium a 0,002 mg/ml; Grupo III (ECA2) - animais tratados com Extrato Concentrado Alcaloídico de Aspidospema pirifolium a 0,004 mg/ml. Foi observado aumento significativo de peso nos animais do grupo (I) e aumento relativo nos animais do grupo (II), enquanto que os animas do grupo (III) não apresentaram alteração significativa de peso no período da prenhez. Aos 20 dias de gestação, quanto ao número de fetos, foram observados os seguintes resultados: Grupo I, média de 4,33 fetos/fêmea; Grupo II, média de 1,33 fetos/fêmea e Grupo III média de 0,00 fetos/fêmea (fêmeas sem fetos). Conclui-se que o extrato concentrado alcaloídico de Aspidospema pirifolium altera a reprodução de ratas, quando administrado do 1º ao 20º dia de prenhez, provocando perda de peso nas fêmeas e diminuição no número de fetos (concentração de 0,002 mg/ml) e perda de peso e ausência de fetos (concentração de 0,004 mg/ml).