Development of Enantioselective Synthetic Routes to (–)-Myrocin G and (–)-Euonyminol.

In the first chapter, I describe the development of a synthetic strategy towards (–)-myrocin G (8), the putative active form of the antiproliferative fungal metabolite (+)-myrocin C (4). Myrocin C (4) has been proposed to cross-link DNA by two-fold nucleotide addition; however, this proposed bioalkylation hypothesis has not been tested with native DNA. Our synthetic efforts provided a highly convergent total synthesis of myrocin G (8) in 15 steps from simple starting materials. A key steps in the sequence involved a carefully designed fragment coupling–cyclization cascade (see 85 + 89 → 90). This transformation effectively unites the iodocyclopropane 85 with the enoxysilane 89 to provide in a single step and in 38% yield the protected form of the target. Next, I present our preliminary biological activity studies of the diosphenol (–)-myrocin G (8) including DNA cleavage and DNA cross-linking studies. The data collected from these studies indicates that myrocins do not cross-link or cleave DNA and rather suggests an alternative mode of action potentially involving a protein target. In the second chapter, I present the development of an enantioselective synthesis of the heavily oxidized sesquiterpenoid (–)-euonyminol (99). Euonyminol (99) is the dihydro-β-agarofuran nucleus of the macrocyclic terpenoid alkaloids known as the cathedulins. This natural product is characterized by a tricyclic framework comprising of a trans-decalin fused to a tetrahydrofuran ring and by possessing nine free hydroxyl groups. Our synthetic route to access euonyminol features several highly diastereoselective transformations that were specifically designed to overcome problems encountered. For example, we developed a metal catalyzed [3+2] dipolar cycloaddition reaction provided the vinylogous carbonate 147 and simultaneously established the C9 oxidation and the C10 quaternary stereocenter, a tandem lactonization–epoxide opening to form the trans-C2–C3 vicinal diol residue, and a late-stage diastereoselective α-ketol rearrangement necessary for the syn-C8–C9 oxidation pattern. The body of work presented in this chapter may set the stage for synthesizing the macrocyclic cathedulin alkaloids, such as cathedulin E-4 (104)

PRELIMINARY DESIGN OF AN X-RAY IMAGING SYSTEM FOR THE BONE STRUCTURAL INDEX EVALUATION

Osteoporosis (OP) is a very common disease in which the bones become weak and are more likely to break. Despite the huge costs in the EU and worldwide, the majority of individuals who have sustained an osteoporosis-related fracture or who are at high risk of fracture are left untreated. In effect, OP is a silent disease, with bones deteriorating without warning until fracture, and the current screening modalities are not significantly better than age alone, also because they consider only the bone quantity (bone mineral density, BMD) and the clinical risk factors, but disregard the bone quality, that is the structural soundness of the trabecular arrangement, which can be evaluated by simulations on virtual models. While 3D models can only be used in research because of high costs, an alternative approach based on the acquisition of planar hand radiograms for bone behaviour simulations, and the use of a Structural Index, SI, for bone quality ranking, have been developed at the University of Trieste. In this work, we discuss the preliminary design of a portable low dose X-ray hand scanner to be used as a low cost, user-friendly device (Fig.1) for imaging the trabecular pattern in the proximal phalanges of the non-dominant hand and for providing a radiogram suitable for the SI evaluation

PRELIMINARY DESIGN OF AN X-RAY IMAGING SYSTEM FOR THE BONE STRUCTURAL INDEX EVALUATION

Osteoporosis (OP) is a very common disease in which the bones become weak and are more likely to break. Despite the huge costs in the EU and worldwide, the majority of individuals who have sustained an osteoporosis-related fracture or who are at high risk of fracture are left untreated. In effect, OP is a silent disease, with bones deteriorating without warning until fracture, and the current screening modalities are not significantly better than age alone, also because they consider only the bone quantity (bone mineral density, BMD) and the clinical risk factors, but disregard the bone quality, that is the structural soundness of the trabecular arrangement, which can be evaluated by simulations on virtual models. While 3D models can only be used in research because of high costs, an alternative approach based on the acquisition of planar hand radiograms for bone behaviour simulations, and the use of a Structural Index, SI, for bone quality ranking, have been developed at the University of Trieste. In this work, we discuss the preliminary design of a portable low dose X-ray hand scanner to be used as a low cost, user-friendly device (Fig.1) for imaging the trabecular pattern in the proximal phalanges of the non-dominant hand and for providing a radiogram suitable for the SI evaluation

Suicide among adolescents in Brazil: public health problem?

Universidade Federal de São Paulo (UNIFESP) Departamento de PsicobiologiaUniversidade Federal de São Paulo (UNIFESP) Departamento de PsiquiatriaUNIFESP, Depto. de PsicobiologiaUNIFESP, Depto. de PsiquiatriaSciEL

Social representations and directing to the environmental education in the Perobas Biological Reserve, State of Paraná, Brazil

The Perobas Biological Reserve is situated in the Brazilian municipalities of Tuneiras do Oeste and Cianorte, State of Paraná. Prior to the foundation, the local and state communities’ representatives manifested different standpoints, favorable and unfavorable, concerning the establishment of this environmental protection area. Considering the importance of comprehending social representations that students from the City of Tuneiras do Oeste have concerning the Perobas Biological Reserve, the present study aimed at investigating Basic Education students, as well as indicating ways for an environmental education development. We used the Free Evocation of Words technique and the analysis of composition contents. We identified that representations of the analyzed group are based on the Nature components present in the Reserve and on the role of the local inhabitants for their conservation, however such knowledge is not well-founded. We understand that educative actions must be initiated in order to proportionate the construction of knowledge concerning the Reserve´s Nature components and the mutual interactions involved. This knowledge can, subsequently, lead students to comprehend that a role is ascribed to them in the protection and the co-responsibility for the preservation of the protected area

Memórias do Exílio: deslocamentos e experiências de um exilado republicano espanhol

Esta comunicação vincula-se à tese em desenvolvimento que contempla a trajetória de luta e o exílio de Pedro Brillas (1919-2006), um ex-combatente republicano da Guerra Civil Espanhola, que levado pelas circunstâncias, viu-se exilado definitivamente em 1939, assim como milhares de espanhóis

La Retirada (1939) e o exílio republicano no Camp d’Argelès-sur-Mer (França) na narrativa autobiográfica de um exilado espanhol

Este artigo objetiva rastrear a trajetória e as experiências de um ex-combatente da Guerra Civil Espanhola, por intermédio das memórias de Pedro Brillas (1919-2006), que refletem vivências pessoais e coletivas, durante o êxodo republicano espanhol rumo à França, conhecido como La Retirada, e o exílio inicial dos refugiados no Camp D’Argelès-sur-Mer, em 1939, em consequência da iminente derrota antifranquista, no fim da guerra. Por meio da narrativa autobiográfica do memorialista, estabelece-se um diálogo vívido com a historiografia contemporânea, espanhola e francesa, retratando dramas, adversidades e incertezas de milhares de retirantes espanhóis. Além disso, em seus escritos, afloram sensibilidades pessoais.  O corpus documental é constituído dos textos autobiográficos de Pedro Brillas, composto de memórias, diários (inclusive da frente de batalha), cartas, entre outros. O precioso acervo relata experiências cotidianas e incomuns, subjetividades, além dos deslocamentos dos exilados espanhóis, vivenciados coletivamente. Geralmente guardados em baús e gavetas, esses materiais de e/imigrantes recuperam e atualizam a memória individual e coletiva, representam um tesouro documental da produção de populares, muitas vezes invisível, que ganharam valor na historiografia

Direito de Águas no Brasil

Divulgação dos SUMÁRIOS das obras recentemente incorporadas ao acervo da Biblioteca Ministro Oscar Saraiva do STJ. Em respeito à lei de Direitos Autorais, não disponibilizamos a obra na íntegra. Localização: 347.247(81) P788d Código de barras: STJ00064649 STJ00084571 2.ed