The organic extracts of Formosan soft coral Cladiella australis, collected along the coast of Kenting, Taiwan. Investigation on C. australis has led to the isolation of ten compounds 1-10, including six new compounds, australin A (1), australin B (2), australin C (3), australin D (4), (24S)-3£]-acetoxy-24-methylchloest-5-en-21-oic acid (6)¡Bcladiosulfone (10), and three compounds were first isolated from the natural sources, 5'-acetylthymidine (7), 2'-deoxy-3'-O-acetylthymidine (8), p-vinylbenzyl alcohol (9), and one know compounds (24S)-3£] -hydroxy-24-methylchloest-5-en-21-oic acid (5). Structures of these compounds were determined on the basis of spectroscopic evidences (including MS, IR, 1D and 2D NMR). Cytotoxicity of these compounds toward various cancer cell lines has also been determined.

Köln, Universiẗat, Diss., 2002.

No description available.

The marine diterpene (–)-stolonidiol (1) has been shown to upregulate neuronal levels of acetylcholine. The mechanism through which a small molecule can impart this allosteric-like effect is currently unknown. A laboratory preparation of the natural product was undertaken in order to produce matieral for biological testing and elucidation of the unknown mechanism of action. During the course of this study, a tandem enyne-Suzuki reaction was investigated to form both rings of the fused bi-cyclic structure 26 in a single operation, but was met with undesired diastereoselectivity in the first cyclization step. The directing effect was found to be general on 1,6-homopropargyl enynes. Further efforts toward the molecule focused on an enantioselective formation of the cyclopentane core through an extension of a copper-mediated silylcyclization of epoxyalkyne 71. Using this intermediate two routes involving acrylate as a lynchpin to close the large ring were investigated. Additionally, a route designed to employ an intramolecular Knoevenagel condensation was explored to generate this ring system. / text

No description available.

<p> The C-B-A ring formation sequence has been adopted towards a total synthesis of podocarpic acid starting from 2, 7-dihydroxynaphthalene. Experimental procedures which were developed by other workers have been modified to improve the yields and the purity of the products. </p> <p> Using naturally occurring podocarpic acid, a reliable procedure has been explored for the functionalization of C-6 and C-7 positions in order to construct the 19,6-lactone ring in synthetically satisfactory yields. Catalytic reduction of the aromatic ring C, after functionalization of ring B, has been investigated with the aim of developing a pathway towards the elaboration of the C, D ring system of the kaurane skeleton. </p> / Thesis / Doctor of Philosophy (PhD)

Mass spectrometry was used in conjunction with numerous 1-D and 2-D NMR techniques to determine the structures, devoid of stereochemistry, of five different compounds isolated from the extracts of Eunicea succinea, Eunicea tourneforti, and an unidentified species isolated from the Eunicea genus by Professor Meledath Govindan, of the University of the Virgin Islands. Three of the compounds were then identified as the known compounds eunicin, 12,13-bisepieupalmerin, and 7(S),8(S)-epoxy-1(S),11(R)-dolabella-3E,12(18) -dien-13-one by comparison of their spectroscopic data and optical rotations with those published in the literature. Optical rotations could not be measured accurately for the other two compounds because of small sample sizes; therefore, another method had to be found to elucidate the stereochemistry of these two structures. To solve this problem, molecular modeling and NOESY were employed. Comparison of the NOESY interactions to the thermodynamically available conformations of several possible stereoisomers, calculated by molecular modeling, proved to be a useful technique. One of the remaining two structures was identified as the known stereoisomer euniolide. The stereochemistry of the one remaining structure could not be assigned because sample size was not large enough to obtain a clean NOESY spectra. Finally, based on published synthetic work by Corey and Kania, the absolute stereochemistry of the dolabellane was revised to 7(R),8(R)-epoxy-1(R),11(S)- dolabella-3E,12(18)-dien-13-one. / Master of Science

Introdução: A hipertensão arterial sistêmica (HAS) é uma condição clínica multifatorial caracterizada por níveis elevados e sustentados de pressão arterial. Nos últimos anos, estudos demonstraram o efeito cardiovascular de diversos metabólitos originados de várias espécies de plantas. O diterpeno é um exemplo, o qual age por meio de diversos mecanismos farmacológicos. Sabendo que o Manool pertence a esta classe de compostos, isso o torna uma substância com potencial uso no tratamento da HAS, motivo pelo qual se propôs o desenvolvimento deste trabalho. Objetivos: 1) Avaliar in vivo o possível efeito vasodilatador de diferentes doses do Manool e o efeito sobre os níveis plasmáticos de óxido nítrico (NO), em animais normotensos e hipertensos e; 2) Verificar in vitro os mecanismos endoteliais envolvidos na resposta de relaxamento, em anéis de aorta de ratos. Material e métodos: Os animais foram divididos aleatoriamente em dois grupos: hipertenso e normotenso. Os animais do grupo hipertenso foram submetidos ao procedimento cirúrgico 2R1C para indução de hipertensão, enquanto os animais do grupo normotenso foram sham-operados. A pressão arterial (PA) não-invasiva, foi mensurada utilizando-se um manguito, conectado a um sensor para registro de PA, colocado em torno da cauda do animal. Para identificar os efeitos in vivo do composto, três doses do composto foram aplicadas nos animais, a monitorização invasiva da PA foi realizada por meio do MP System 100 A. Para a medida do óxido nítrico (NO) plasmático, foi utilizada a técnica de quimiluminescência NO/ozônio (O3). Com intuito de observar os mecanismos envolvidos no relaxamento induzido pelo composto, curvas concentração-resposta para o Manool, foram obtidas em anéis de aorta com e sem endotélio, na presença e ausência de L-NAME e ODQ. Resultados: Os resultados sobre a ?PAS mostrou que o Manool, promoveu redução da PAS tanto em normotensos quanto hipertensos. Os resultados das curvas dose-resposta mostraram que o manool promoveu relaxamento Resumo dependente do endotélio e este foi inibido na presença de L-NAME e ODQ. Não foi observado diferença na dosagem de NOx. Conclusão: Em resposta aos objetivos propostos para a presente investigação pode-se concluir que o Manool é uma droga hipotensora, possivelmente dependente em grande parte da função endotelial via NO/cGMP. / Introduction: Systemic hypertension (SH) is a multifactorial clinical condition characterized by high and sustained levels of blood pressure. In recent years, studies have demonstrated the cardiovascular effect of various metabolites derived from many plant species. The diterpene is an example, which acts through different pharmacological mechanisms. The Manool belongs to this class of compounds, that makes a substance with potential use in the treatment of SH, which let us to propose the development of this work. Objectives: 1) To evaluate in vivo the possible vasodilator effect of different doses of Manool and the effect on the plasma levels of nitric oxide (NO) in normotensive and hypertensive animals; 2) Evaluate in vitro endothelial mechanisms involved in the relaxation response in rat aortic rings. Material and methods: The animals were randomly divided in two groups: normotensive and hypertensive. The animals of the hypertensive group underwent the surgical procedure 2K1C for hypertension induction, while the animals of the normotensive group were sham-operated. The blood pressure (BP) non-invasive, was measured using a cuff, connected to a sensor for registration BP, placed around the animal\'s tail. To identify the in vivo effects of the compound, three doses of the compound were applied in animals, invasive BP monitoring was performed using the System MP 100 A. For the measurement of NO plasma, we used the technique of chemiluminescence NO/ozone (O3). In order to observe the mechanisms involved in the relaxation induced by compound concentration-response curves for Manool were obtained in the aorta rings with and without endothelium in the presence and absence of L-NAME and ODQ. Results: The results on variation of systolic blood pressure (?SBP) showed that Manool, decreases the SBP in both normotensive as hypertensive. The results of the dose-response curves showed that the Manool promoted endothelium dependent relaxation and this was inhibited in the presence of L-NAME and ODQ. There was no difference in NOx dosage. Conclusion: In response to the proposed Abstract objectives for the present investigation may conclude that the Manool is a hypotensive drug, possibly dependent in large part on endothelial function NO / cGMP pathway.

In the course of studying on secondary metabolites from marine organisms, we have investigated the chemical constituents of the soft coral Sarcophyton ehrenbergi collected at San-Hsien-Tai, Taitong County, Taiwan. Chromatographic separation of the organic extracts has led to the isolation of nine new cembrane diterpenes 1¡V9, and a initial natural separation of known cembrane diterpene 10. The chemical structures of pure compounds were determined by spectral (NMR, MS, UV and IR) and physical data, as well as comparison with the spectroscopic data of related chemicals in literature. Moreover, the metabolites 1¡V10 were evaluated in vitro for their cytotoxicity against of A-549 (human lung epithelial carcinoma), HT-29 (human colon adenocarcinoma), and P-388 (mouse lymphocytic leukemia) cells, as well as anti-HCMV activity. Compounds 3, 6, 9, and 10 were shown to exhibit significant cytotoxicity activities against P-388 with ED50 values of 2.7, 3.6, 2.0, and 3.0 £gg/mL, respectively. Compound 1, 2, 3, and 7 exhibited inhibitory activity against anti-HCMV, with EC50 values of 60.0, 46.0, 5.0, and 45.0 £gg/mL.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A desacetilnemorona (HCRH) Ã um diterpeno abietano com anel para-quinona em sua estrutura, sendo entÃo classificada como tanshinona que sÃo frequentemente descritas pelo seu amplo espectro de atividades biolÃgicas. O diterpeno HCRH foi isolado e identificado pela primeira vez em 1971 a partir das raÃzes de plantas do gÃnero Salvia, no entanto sua atividade biolÃgica ainda nÃo havia sido descrita previamente. O objetivo deste trabalho foi avaliar o potencial anticÃncer da desacetilnemorona isolada das raÃzes da planta Hyptis carvalhoi. O presente estudo avaliou o potencial citotÃxico do diterpeno HCRH em vÃrias linhagens de cÃlulas tumorais e normais pelo teste do MTT e seu possÃvel mecanismo de aÃÃo. ApÃs 72 horas de incubaÃÃo, o composto testado apresentou valores de CI50 que variaram de 3,91 a 32,01 ÂM em cÃlulas tumorais de cÃlon (HCT-116) e leucÃmicas (HL-60), respectivamente. Enquanto que para cÃlulas normais esses valores foram de 35,68 ÂM para a linhagem V-79 e maiores que 72 ÂM para linhagens 3T3-L1 e CMSP. Em cÃlulas tumorais de cÃlon (HCT-116), o diterpeno mostrou potencial antiproliferativo de maneira tempo-dependente, induzindo aumento do nÃmero de cÃlulas na fase G0/G1 do ciclo celular e uma diminuiÃÃo expressiva da sÃntese de DNA. Esses efeitos foram acompanhados por alteraÃÃes nos nÃveis de ciclinas e CDKs, alÃm do aumento nos nÃveis das proteÃnas p21waf1/cip1 e p27kip1, independente da ativaÃÃo de p53. Dentre os eventos iniciais induzidos pelo diterpeno HCRH estÃo a geraÃÃo de espÃcies reativas de oxigÃnio (EROs) e a induÃÃo de dano ao DNA, com posterior ativaÃÃo das vias de morte. Com isso podemos sugerir que a desacetilnemorona apresenta potente atividade antiproliferativa que provavelmente se inicia com a geraÃÃo de EROs levando ao dano de DNA, o que impede a progressÃo do ciclo celular e encaminha as cÃlulas aos processos de morte por apoptose e autofagia. / The desacetylnemorone (HCRH) is an abietane diterpene with para-quinone ring in its structure, and then classified as a tanshinone that are often described by their broad spectrum of biological activities. The diterpene HCRH was isolated and identified for the first time in 1971 from roots of plants of the genus Salvia, however its biological activity has not been yet fully characterized. The aim of this study was to evaluate the anticancer potential of desacetylnemorone isolated from the roots of the plant Hyptis carvalhoi. The present study evaluated the cytotoxic potential of the diterpene HCRH in several tumor and normal cell lines using the MTT assay and its possible mechanism of action. After 72 hours of incubation, the tested compound showed IC50 values ranging from 3.91 to 32.01 ÂM in colon tumor (HCT-116) and leukemic (HL-60) cells, respectively. While for normal cells IC50 values ranged from 35.68 ÂM in V-79 to higher than 72 ÂM in 3T3-L1 and PBMC cells. In colon tumor cells (HCT-116), the diterpene showed antiproliferative potential of time-dependent manner, leading to increased number of cells in the G0/G1 phase of the cell cycle and a substantial decrease in DNA synthesis. These effects were accompanied by changes in the levels of cyclins and CDKs, in addition to the increase in the levels of proteins p21waf1/cip1 and p27kip1, independent of p53 activation. Among the initial events induced by diterpene HCRH are the generation of reactive oxygen species (ROS) and the induction of DNA damage with subsequent activation of death pathways. Thus, we can suggest that desacetylnemorone has potent antiproliferative activity associated with ROS generation leading to DNA damage, which prevents cell cycle progression and drive cells to the process of death by apoptosis and autophagy.