Thesis (M.S.)--University of Wisconsin--Madison, 1935. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves i-ii).

Thesis (Ph. D.)--Ohio State University, 2005. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2006 Sep 19

Thesis (M.Phil.)--Hong Kong University of Science and Technology, 2008. / Includes bibliographical references.

The patellazoles are a family of marine polyketide natural products first isolated from Lissoclinum patella in 1988 by both the Moore and Ireland groups. They exhibit significant cytotoxicity against the HCT 116 human colon tumour cells. To date however, their full 3D stereostructure have yet to be elucidated, which has hindered their development as potential drugs, and hampered full investigation into their biological mechanism of action and has deterred total synthesis efforts. This thesis describes synthetic efforts towards Patellazole B, which exhibits the highest potency of the three main congeners. To fully elucidate the structure and renew interest in the patellazoles as anticancer compounds, we have developed a flexible and modular synthesis that aims to define the unknown stereocentres within the pertinent region and allow for rapid fragment union. Compound 36 has been chosen as an initial target for NMR comparison studies. The synthesis of all eight diastereomers of this macrocycle should aid determination of the four unknown stereocentres. Chapter 2 describes the synthesis of the C1–C12 fragment, focusing on the configuring of the C5 methyl stereocentre and the construction of the C7-C10 stereotetrad via a boron-mediated anti aldol with an in-situ reduction. In the third chapter, the synthesis of the C13-C19 fragment is outlined. A boron-mediated glycolate aldol has been used to install the C16-C17 anti stereochemistry and a substrate-controlled reduction at C15 delivered the hydroxyl with high diastereoselectivity. Studies into the C¬17¬ methylation are also described. Chapter 4 describes the synthesis of one possible diastereomer of the C20-C25 fragment, as a template for the preparation of the other 7 possible diastereomers. The route therefore employs only catalyst based control methods to install the three stereocentres, utilising a Sharpless asymmetric epoxidation and Evans aldol to construct the stereotriad. The 22R, 23S, 24S diastereomer has been initially chosen to investigate the later chemistry. Chapter 5 contains discussion of the ongoing work investigating fragment union and formation of the macrocycle. A Heck coupling reaction has been employed to construct the C19-C20 bond and a Suzuki coupling reaction has been developed to facilitate the C12-C13 bond formation. These two cross couplings have delivered the C1 - C25 fragment, 360, the final compound reported in this thesis, which is three steps away from the completed macrocycle and six from compound 36. The experimental procedures and spectroscopic characterisation of the synthesised intermediates can be found in Chapter 6 and the Appendix.

No description available.

Seaweed has traditionally been used in Scotland and other countries both as food and for medicinal purposes, which has led to seaweed being investigated for their natural product content. Despite over 30 years of research, the majority of species found in Scotland have yet to have their chemistry examined. Extracts of seaweed were tested for antimicrobial activity against marine bacteria. Extracts of Palmaria palmata, Ulva linza, Chondrus crispus and Pelvetia canaliculata showed no detectable activity, while ethyl acetate extracts of Fucus serratus, Halidrys siliquosa, Osmundea pinnatifida and Polysiphonia fucoides showed activity against at least six of the seven strains. Extracts were screened for radical scavenging activity against ABTS, DPPH and superoxide radicals. At least one extract from each brown seaweed showed radical scavenging of at least 80 % towards ABTS+ with an ethyl acetate extract of P. fucoides and H siliquosa quenching DPPH by at least 90%. Radical scavenging activity appears to be dependent total phenolic content of extract. Extracts were subjected to a series of assays relevant to human health. Ethyl acetate extracts showed high antiparasitic activity against Trypanosoma brucei with a P. fucoides extract showing antibacterial activity toward Staphylococcus aureus. Extracts of H siliquosa and F. serratus showed cytotoxicity to Hela cells with extracts of H siliquosa showing cytotoxicity to LN CAP AS and PC 3 cell lines. An extract of H siliquosa underwent chromatography and by applying assay guided fractionation, several active fractions were identified. These were analysed using NMR and LC/MS and four compounds identified: (2E. 6E. 14E)-1-(l'-hydroxy-4'-methoxy-6'-methyl- phenyl)-5, 13-dihydroxy-12-one-3, 7, 11, 15-tetramethylhexadeca-2, 6, 14-triene, a known antibacterial compound, previously identified in H siliquosa; (2E, 6E, 10E, l4E)-1-(1'- hydroxy-4'-methoxy-6'-methyl phenyl)-5, 12 dihydroxy-3.7, 11, 15-tetramethyl hexadeca- 2.6, 10, l4-tetraene, previously identified in Cystoseira elegans, and now in H siliquosa; and two compounds that have not been reported before.

O fato de esteróides de plantas apresentarem tanto funções fisiológicas quanto ecológicas, talvez tenha sido fator limitante de seu uso em quimiossistemática. Até hoje, os trabalhos do nosso grupo têm se restringido a marcadores com apenas funções ecológicas. Neste trabalho, utilizamos esteróides como marcadores quimiossistemáticos, com o intuito de descobrir se eles poderiam ser analisados com a metodologia usual desenvolvida por nosso grupo. Devido à ampla distribuição dessas moléculas, limitamos o trabalho a angiospermas. Inicialmente, realizamos um levantamento bibliográfico no Chemical Abstracts (até dezembro de 1986) e, em uma segunda etapa, codificamos e armazenamos os dados em um microcomputador IBM-PC. A presença de alguns esteróis (campesterol, sitosterol, colesterol e estigmasterol) em praticamente todos organismos, levou-nos a eliminar deste trabalho esse grupo de substâncias, pois características imutáveis não têm valor quimiossistemático. Baseados em semelhanças estruturais, separamos os esteródes em oito tipos, a saber: esteróides, brassinolídeos, ecdisonas, sapogeninas, witanolídeos, pregnanos, cardenolídeos e bufodienolídeos. Esta classificação foi legitimada por análises estatísticas (testes não-paramétricos). Os índices de oxidação e especialização de esqueleto (metodologia do nosso grupo) não revelaram muitas diferenças dentro de cada tipo esteroidal. De um modo geral, estes tipos esteroidais apresentam-se predominantemente distribuídos em certos grupos de angiospermas. Este é, por exemplo, o caso das ecdisonas em Caryophyllales e Lamiales, dos witanolídeos em Solanales e, dos cardenolídeos e pregnanos em Gentianales. Por outro lado, enquanto superordens, como Magnoliiflorae, apresentam apenas esteróis (tipo menos oxidado e menos especializado), outras superordens, como Ranunculiflorae, Solaniflorae e Liliiflorae, apresentam uma fantástica diversidade de tipos. As monocotiledôneas se caracterizam pela presença de saponinas, e os outros tipos (exceto esteróis) aparecem com distribuição esparsa. Comparando nossos dados com os de pteridófitas gimnospermas (apenas esteróis e ecdisonas), podemos concluir que a diversidade dessa classe de micromoléculas em angiospermas coloca os esteróides na posição de uma característica evoluída de plantas. / Plant steroids perform not only ecological, but also physiological functions. Hence it was thought a priori that their use as chemosystematic markers should be of doubtful value. The present work aimed to evaluate the correctness of this concept. In view of the vast natural distribution of steroids we restricted our efforts to the angiosperms. Initially we undertook a literature survey in Chemical Abstracts (up to 1986) and then we codified and stored the data in a microcomputer IBM-PC. Some of the steroids (campesterol, colesterol, sitosterol and stigmasterol) occur practically in alI organisms. Since constant characters are of little systematic value, such compounds were omitted from our study. According to structural analogies we separated plant steroids in eight types: simple steroids, brassinolides, ecdysons, sapogenins, withanolides, pregnanes, cardenolides and bufodienolides. This classification was authenticated by statistical analyses (non parametric tests).The skeletal speciaIizations and the oxidation levels (according to methodology developed by our group) did not differ greatly wthin each steroidal group. However the general distribution of steroids in angiosperms is quite selective. This is the case e.g. for ecdysons in Caryophyllales and Lamiales. On the other hand, while superordens such as Magnoliiflorea are characterized only by steroids (the least specialized and oxygenated type), other superordens such as Ranunculiflorae, Solaniflorae and Liliiflorae are characterized by a very considerable number of types. The monocotyledons contain chiefly saponins, other types (except steroids) appearing more sparsly distributed. In contrast to angiosperms pteridophytes and gymnosperms posses only few steroidal types (simple steroids and ecdysons). Hence diversity of this micromolecular class is an indication of phylogenetic advance in the plant kingdom.

Resumo: Este trabalho apresenta a aplicação da metodologia de análise in silico em frações da partição líquido-líquido obtidas a partir do extrato hidroalcoólico das folhas de Ocotea paranapiacabensis e Aniba firmula (Lauraceae). A abordagem utilizou os dados obtidos a partir da técnica hifenada CLAE-DAD-IES-EM, sendo esses dados analisados e contrastados com a base de dados do Dictionary of Natural Products (DNP), a fim de se detectar metabólitos secundários previamente isolados nos gêneros Ocotea e Aniba. A partir da obtenção desses dados, foi possível direcionar o estudo das frações analisadas para a identificação de novas substâncias nos gêneros estudados. Utilizando a metodologia, foram detectadas, estruturas isoméricas de alcalóides aporfinóides e dois flavonóides monoglicosilados nas folhas de O. paranapiacabensis. Não há relatos desses flavonóides em espécies do gênero Ocotea, o que levou ao planejamento de uma estratégia para o isolamento desses constituintes, que tiveram sua estrutura elucidada através da análise de RMN 1H e 13C. A abordagem utilizada no estudo da fração acetato de etila das folhas de A. firmula possibilitou a detecção de quatro substâncias da classe das estirilpironas (1- 4), esses dados foram importantes para a obtenção de uma região específica do perfil cromatográfico CLAE-DAD onde não foram detectados substâncias previamente isoladas através da análise in silico. A fração AFFAc foi então submetida a CLAE-UV com a finalidade de identificar novos constituintes químicos (estirilpironas). A fração obtida foi analisada e purificada, resultando no isolamento de dímeros de estirilpironas inéditos na literatura, 4-metoxi-8'-(11',12'- metilenodioxifenil)-7-[6-(4-metoxi-2-pironil)]-6'-estiril-oxabiciclo[4,2,0]-ocat-4'-em-2'- ona (5) 8'-(11', 12'metilenodioxifenil)-8-fenil-7,7' di [6-(4,4'-dimetoxi-piran-2-ona) ciclobutano... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This work presents the application of the methodology in silico in partition liquid-liquid fractions obtained from the hydroalcoholic extract of leaves of Ocotea paranapiacabensis and Aniba firmula (Lauraceae). The approach used the data obtained from the hyphenated technique HPLC-DAD-ESI-MS, these data are analyzed and contrasted with the database of the Dictionary of Natural Products (DNP) in order to detect secondary metabolites previously isolated in the genus Ocotea and Aniba. Upon obtaining these data, it was possible to direct the study of fractions analyzed to the identification of new substances in the genera studied. Using the methodology, were detected, isomeric structures of aporphinic alkaloids and two flavonoids in leaves of O. paranapiacabensis. There are no reports of these flavonoids in species of the genus Ocotea, which led to planning a strategy for the isolation of these constituents, which had its structure elucidated by analysis of 1H and 13C NMR. The approach used in the study of the ethyl acetate fraction of leaves of A. firmula enabled the detection of four substances of styrilpyrones class (1-4), these data were important for determination a specific region of the HPLC-DAD chromatographic profile which were not detected substances previously isolated by in silico analysis. The fraction AFFAc was then subjected to HPLC-UV with the aim of identifying new chemical constituents (styrilpyrones). The fraction obtained was analyzed and purified, resulting in the isolation of dimers of estirilpironas unprecedented in the literature, 4-methoxy-8 '- (11', 12 '-metilenodioxiphenyl) -7 - [6 - (4-methoxy-2-pironil) ] -6 '-styryl-oxabicyclo [4,2,0]-ocat-4'-at-'2-one (5) 8' - (11 ', 12' metilenodioxiphenyl)-8-phenyl-7, 7'- di [6 - (4,4 "-dimethoxy-pyran-2-one) ciclobutane (6), confirming the importance of application of in silico analysis as a tool for the identification of chemical constituents in the already described species. / Orientador: Vanderlan da Silva Bolzani / Coorientador: Ian Castro-Gamboa / Banca: Alberto José Cavalheiro / Banca: Patrícia Mendonça Pauletti / Mestre

Orientador: Ian Castro-Gamboa / Banca: Lucia Xavier Lopes / Banca: Maria Inês Genovese Rodriguez / Resumo: O Núcleo de Bioensaios, Biossíntese e Ecofisiologia de Produtos Naturais (NuBBE) condensa, em suas atividades de pesquisa, o estudo de micromoléculas bioativas provenientes de plantas do Cerrado e Mata Atlântica Paulistas. Nos últimos anos o NuBBE investe no desenvolvimento de metodologias analíticas de derreplicação, utilizando diversas técnicas acopladas, tais como, CLAE/DEQ-DAD, EMAR/CLAE-DAD e EM/CLAE-DAD, para acelerar a escolha de extratos vegetais brutos. Técnicas analíticas de detecção in silico vêm sendo incorporadas às metodologias cromatográficas de construção de perfis micromoleculares, auxiliando na seleção apenas dos metabólitos de interesse presentes em matrizes brutas. Nesta dissertação foi abordado o estudo dos extratos de Strychnos brasiliensis e S. pseudoquina (Loganiaceae) através de bioensaios de atividade antioxidante e de inibição de polimerização da hematina. Esses bioensaios revelaram a fração acetato de etila, dos galhos de S. brasiliensis, como matriz promissora em ambos os testes assim como os galhos de S. pseudoquina com potencial atividade antioxidante. A fração acetato de etila dos galhos de S. brasiliensis e o extrato bruto das folhas de S. pseudoquina foram avaliados fazendo uso da técnica hifenada EMAR/CLAE-DAD. Como resultado desta análise, quatro micromoléculas foram elucidadas: a 10- hidroxi-17-O-metilacagerina para as folhas de S. pseudoquina, estricnohirsutina, 14,15,16-trinor-11-labden-13,8-oleído e acagerina para a fração acetato de etila dos galhos de S. brasiliensis. Além disso, foi construída uma base de dados que reúne algumas informações físico-químicas e espectroscópicas valiosas, ajudando na detecção e isolamento das substâncias presentes nas duas espécies de Strychnos, objeto do nosso estudo. / Abstract: The Nuclei of Bioassays, Biosynthesis and Natural Products Ecophysiology (NuBBE) condenses in their research activities, the study of bioactive micromolecules from plants of the Cerrado and Atlantic Forest from São Paulo's State. In recent years, NuBBE has increased efforts in the development of analytical dereplication methods using various coupled techniques such as HPLC/DAD-ECD, EMAR/DAD and HPLC-MS/HPLC-DAD, to speed-up the selection of crude plant extracts. In silico analytical techniques have been incorporated into chromatographic methodologies aiming to build micromolecular profiles, assisting in the selection only of metabolites of interest in crude matrixes. This dissertation aims the study of extracts from Strychnos brasiliensis and Strychnos pseudoquina (Loganiaceae) throughout bioassays of antioxidant activity and inhibition of polymerization of heme, which showed the ethyl acetate fraction from branches of S. brasiliensis, as a promising matrix in both in vitro tests as well as the branches of S. pseudoquina that showed potential antioxidant properties. The ethyl acetate fraction from Strychnos brasiliensis branches and the crude extract from leaves of Strychnos pseudoquina were evaluated using HRMS/HPLC-DAD. From that analysis, four structures have been elucidated: 10-hydroxy-17-O-methylakagerine, from leaves of S. pseudoquina, strychnohirsutine, 14,15,16-trinor-11-labden-13,8-olide and akagerine from the ethyl acetate fraction of branches from S. brasiliensis. In addition, we have built up a database that gathers information about the structures detected in this study, such as molecular weight, structure, molecular formula, mass spectrum, aiming to facilitate the structural as well as the total elucidation of molecules of interest. / Mestre

Resumo: No trabalho foi abordado o estudo de extratos do fungo Phomopsis stipata cultivado em diferentes meios de cultura na implementação da metodologia in silico utilizando cromatografia gasosa acoplada à espectrometria de massas e cromatografia líquida de alta eficiência acoplada à espectrometria de massas de alta resolução conjugados com a base de dados do dicionário de produtos naturais (http://dnp.chemnetbase.com). Foi realizada a comparação da diversidade na produção metabólica do fungo endofítico quando cultivado em diferentes meios de cultura comerciais e em cereal (milho), através do perfil cromatográfico, assim como avaliação das atividades antioxidante e propriedades de inibição da polimerização do heme. Nos extratos diclorometânicos foram identificadas oito substâncias. No extrato diclorometânico do fungo endofítico, crescido em milho, cinco substâncias foram detectadas, sendo elas: 1- derivado -lactônico; 2- ácido n-hexadecanóico; 3- ácido 16-octadecanóico; 4- di-hexanoato de 2-etilhexila e 5- hexadecanoato de iso-propilodiol. E, para o extrato diclorometânico de P. stipata, crescido em meio batata dextrose, três substâncias foram detectadas, dentre elas: 6- ciclohexen-2-ol- 3,5,5-trimetil-ona; 7- hexahidropirrolol [1,2-a] pirazina-1,4-diona-3-benzil e 8- hexahidropirrolol [1,2-a] pirazina-1,4-diona-3-isometil. O emprego de CLAE-DAD-EM e espectrometria de massas tandem possibilitou a identificação, diretamente a partir dos extratos brutos do fungo, de seis substâncias que já foram relatadas para outras espécies do gênero Phomopsis e duas substâncias já antes identificadas na espécie Phomopsis stipata, totalizando oito substâncias detectadas. Para o extrato acetato de etila, crescido em extrato de malte, no modo estático, três substâncias foram detectadas, sendo elas: 10- phomopsidina; 11- phomopsilactona e 12- phomosina... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: This work show the study of extracts of the fungus Phomopsis stipata grown in different culture broth in the implementation of in silico methods using gas chromatography coupled to mass spectrometry and high performance liquid chromatography coupled to mass spectrometer for high resolution, combined with the database dictionary of natural products (http://dnp.chemnetbase.com). A comparison of diversity in the metabolic production of endophytic fungus when grown in different culture broth and cereal (corn) by the chromatographic profile was made, as well as assessment of activities of antioxidant properties and inhibition of heme polymerization. In dichloromethane extracts eight substances were identified. In dichloromethane extract of the endophytic fungus, grown in corn, five substances were detected, which were: 1- -lactone derivative; 2- n-hexadecanoic acid; 3- 16- octadecenoic acid; 4- hexanedioic acid, bis(2-ethylhexyl) ester and 5- hexadecanoic acid, 2-hydroxy-1-(hydroxymetil)ethyl ester, And for the dichloromethane extract of P. stipata, grown on potato dextrose broth, three substances were detected, among them:... (Complete abstract click electronic access below) / Orientador: Ian Castro-Gamboa / Coorientador: Ângela Regina Araújo / Banca: Miriam Sannomiya / Banca: Luce Maria Brandão Torres / Mestre