New routes to enantioenriched substances through small organic molecules

In this thesis we will disclose the results obtained from the diastereoisomeric salt formation (n salt, p salt and p1,n1 salt) between non-racemic trans-chrysanthemic acid (trans-ChA) and pure enantiomers of threo-2-dimethylamino-1-phenyl-1,3-propanediol (DMPP). The occurrence of p1,n1 salt formation can have profound effects on enantiomer separation of scalemic (non-racemic) mixtures. This phenomenon when accompanied by substrate self-association impedes the complete recovery of the major enantiomer through formation of an inescapable racemate cage. A synthetic sequence for the asymmetric synthesis of bicyclo[3.2.0]heptanones and bicyclo[3.2.0]hept-3-en-6-ones through a cycloaddition strategy is reported. The fundamental step is a [2+2]-cycloaddition of an enantiopure amide derived from the reaction between a set of acids and an oxazolidinone as the chiral auxiliary. The inter- and intramolecular cycloaddition of in situ-generated keteniminium salts gives bicycles with a good enantioselection. A key intermediate of Iloprost, a chemically stable and biologically active mimic of prostacyclin PGI2 is synthesized following a ‘green approach’. An example of simple optical resolution of this racemic intermediate involving the diastereoisomeric salt formation is described.

Enantioselective Reactions Promoted by Organocatalytic Species From The Natural Chiral Pool

During the course of my Ph.D. in the laboratories directed by Prof. Alfredo Ricci at the Department of Organic Chemistry “A. Mangini” of the University of Bologna, I was involved in the study and the application of a number of organocatalytic systems, all coming from the natural chiral pool. The first part of this thesis will be devoted to new homogeneous organocatalytic reactions promoted by Cinchona alkaloid-based organocatalysts. Quinine based catalysts were found to be a very effective catalyst for Diels-Alder reactions involving 3-vinylindoles. Excellent results in terms of yields and enantioselectivities were achieved, outlining also a remarkable organocatalytic operational mode mimicking enzymatic catalysis. The same reaction with 2-vinylindoles showed a completely different behaviour resulting in an unusual resolution-type process. The asymmetric formal [3+2] cycloaddition with in situ generated N-carbamoyl nitrones using Cinchona-derived quaternary ammonium salts as versatile catalysts under phase transfer conditions, outlines another application in organocatalysis of this class of alkaloids. During the seven months stage in the Prof. Helma Wennemers’ group at the Department of Chemistry of the University of Basel (Switzerland) I have been involved in organocatalysis promoted by oligopeptides. My contribution regarded the 1,4-addition reaction of aldehydes to nitroolefins. In the work performed at the Department of Organic Chemistry “A. Mangini” of the University of Bologna, in collaboration with the ‘Institut Charles Gerhardt-Montpellier, of Montpellier (France) the possibility of performing for the first time heterogeneous organocatalysis by using a natural polysaccharide biopolymer as the source of chirality was disclosed. With chitosan, derived from deacetylation of chitin, a highly enantioselective heterogeneous organocatalytic aldol reaction could be performed. The use of an eco-friendly medium such as water, the recyclability of the catalytic specie and the renewable nature of the polysaccharide are assets of this new approach in organocatalysis and open interesting perspectives for the use of biopolymers.

Carbon and deuterium isotopes and C ratios in gas hydrates of ODP Leg 204 sites

Sediments at the southern summit of Hydrate Ridge display two distinct modes of gas hydrate occurrence. The dominant mode is associated with active venting of gas exsolved from the accretionary prism and leads to high concentrations (15%-40% of pore space) of gas hydrate in seafloor or near-surface sediments at and around the topographic summit of southern Hydrate Ridge. These near-surface gas hydrates are mainly composed of previously buried microbial methane but also contain a significant (10%-15%) component of thermogenic hydrocarbons and are overprinted with microbial methane currently being generated in shallow sediments. Focused migration pathways with high gas saturation (>65%) abutting the base of gas hydrate stability create phase equilibrium conditions that permit the flow of a gas phase through the gas hydrate stability zone. Gas seepage at the summit supports rapid growth of gas hydrates and vigorous anaerobic methane oxidation. The other mode of gas hydrate occurs in slope basins and on the saddle north of the southern summit and consists of lower average concentrations (0.5%-5%) at greater depths (30-200 meters below seafloor [mbsf]) resulting from the buildup of in situ-generated dissolved microbial methane that reaches saturation levels with respect to gas hydrate stability at 30-50 mbsf. Net rates of sulfate reduction in the slope basin and ridge saddle sites estimated from curve fitting of concentration gradients are 2-4 mmol/m**3/yr, and integrated net rates are 20-50 mmol/m**2/yr. Modeled microbial methane production rates are initially 1.5 mmol/m**3/yr in sediments just beneath the sulfate reduction zone but rapidly decrease to rates of <0.1 mmol/m**3/yr at depths >100 mbsf. Integrated net rates of methane production in sediments away from the southern summit of Hydrate Ridge are 25-80 mmol/m**2/yr. Anaerobic methane oxidation is minor or absent in cored sediments away from the summit of southern Hydrate Ridge. Ethane-enriched Structure I gas hydrate solids are buried more rapidly than ethane-depleted dissolved gas in the pore water because of advection from compaction. With subsidence beneath the gas hydrate stability zone, the ethane (mainly of low-temperature thermogenic origin) is released back to the dissolved gas-free gas phases and produces a discontinuous decrease in the C1/C2 vs. depth trend. These ethane fractionation effects may be useful to recognize and estimate levels of gas hydrate occurrence in marine sediments.

Biscarboxy-Functionalized Imidazole and Palladium as Highly Active Catalytic System in Protic Solvents: Methanol and Water

The coupling reaction between aryl bromides and boron reagents is efficiently catalyzed by an in situ generated palladium complex obtained from palladium(II) acetate (0.1 mol%) and 1,3-bis(carboxymethyl)imidazole (0.2 mol%). The catalytic system is very active in protic solvents, especially in methanol. Biaryl derivatives have been prepared in good isolated yields (up to >99%), and additionally styrene and stilbene derivatives have also been prepared by means of this protocol.

Lipid oxidation kinetics of ozone-processed shrimp during iced storage using peroxide value measurements

In this research, in situ generated ozone exposure/wash cycles of 1, 3, and 5 min applied to shrimp samples either before (BIS) or during iced storage (DIS) has been used to study the lipid oxidation kinetics using the peroxide values (PV). The induction period (IP) as well as PV at end of the IP (PVIP) have been obtained. The rate constants (k) as well as half-lives (t1/2) of hydroperoxides formation for different oxidation stages were calculated. The results showed that both IP and PVIP were lower with BIS (IP between 4.35±0.09 and 5.08±0.23 days; PVIP between 2.92±0.06 and 3.40±0.18 mEq kg−1) compared with DIS (IP between 5.92±0.12 and 6.14±0.09 days; PVIP between 4.49±0.17 and 4.56±0.10 mEq kg−1). The k value for DIS seemed to be the greater compared to BIS. In addition, whilst decreases and increases in t1/2 were found at propagation, respectively, for BIS and DIS, decreases and increases were only found at the induction of oxidation stage(s) for BIS. Further, the PV of ozone-processed samples would fit first order lipid oxidation kinetics independent of duration of ozone exposures. For the first time, PV measurements and fundamental kinetic principles have been used to describe how increasing ozone exposures positively affects the different oxidation stages responsible for the formation of hydroperoxides in ozone-processed shrimp.

Antileishmanial activity of ruthenium(II)tetraammine nitrosyl complexes

The complexes trans-[Ru(NO)(NH(3))(4)L](X)(3) (X = BF(4)(-), PF(6)(-) or Cl(-) and L = N-heterocyclic ligands, P (OEt)(3), SO(3)(-2)), and [Ru(NO)Hedta)] were shown to exhibit IC(50pro) in the range of 36 (L = imN) to 5000 mu M (L = imC). The inhibitory effects of trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3) and of the Angeli`s salt on the growth of the intramacrophage amastigote form studied were found to be similar while the trans-[Ru(NH(3))(4)imN(H(2)O)](2+) complex was found not to exhibit any substantial antiamastigote effect. The trans-[Ru(NO)(NH(3))(4)imN](BF(4))(3) compound, administered (500 nmol kg(-1) day(-1)) in BALB/c mice infected with Leishmania major, was found to exhibit a 98% inhibition on the parasite growth. Furthermore, this complex proved to be at least 66 times more efficient than glucantime in in vivo experiments. (C) 2010 Elsevier Masson SAS. All rights reserved.

Influence of lime type and curing conditions on lime and lime-metakaolin mortars

Durability of Building Materials and Components (Vasco Peixoto de de Freitas, J.M.P.Q. Delgado, eds.), Building Pathology and Rehabilitation, vol. 3, VIII, 105-126. ISBN: 978-3-642-37474-6 (Print) 978-3-642-37475-3 (Online). Springer-Verlag Berlin Heidelberg. DOI: 10.1007/978-3-642-37475-3_5

Role of Intersectoral Collaboration in Mental Health Policy Formulation And Service Delivery in Saint Lucia

RESUMO: Santa Lúcia pequena ilha de país em desenvolvimento com recursos limitados e é confrontada com uma série de desafios socioeconômicos que exigem soluções criativas e inovadoras. É comprovado que a combinação de recursos entre setores para estabelecer os determinantes social, econômico e ambiental da saúde são uma estratégia útil para melhorar a saúde da população, principalmente a sua saúde mental. Este estudo, o primeiro do seu tipo em Santa Lúcia, procurou examinar até que ponto a disponibilidade de uma política nacional de saúde mental levou a ação intersetorial para o fornecimento de serviços e promoção da saúde mental. Além disso, o estudo examinou o nível de colaboração intersetorial que existe entre as agências que prestam cuidados diretos e serviços de suporte para pessoas com doenças mentais e problemas sérios de saúde mental. O estudo também teve como objetivo identificar os fatores que promovem ou dificultam a colaboração intersectorial e gerar recomendações que possam ser aplicadas para países muito pequenos e com perfis socioeconômicos semelhantes. Os dados gerados a partir de três (3) fontes foram sintetizados para formar uma visão ampla das questões. Uma avaliação da política de saúde mental de 2007, uma avaliação que identifica até que ponto a ação intersetorial atualmente deixa a prestação de serviços de saúde mental e a administração de entrevistas semiestruturadas nas mãos de gestores do programa de diferentes agências em todos os setores. O estudo concluiu que, apesar da disponibilidade de uma política de saúde mental, que articula clara e explicitamente a colaboração intersetorial como área prioritária para ação, quase não existe no sistema de fornecimento atual do serviço. Os provedores de serviços em todos os setores reconhecem que há os benefícios da colaboração intersectorial e com entraves significativos em relação à colaboração intersetorial, que por sua vez, impede uma abordagem nacional para o planejamento e o fornecimento do serviço. A colaboração intersetorial não será possível se os próprios setores dependerem da abordagem direta do setor da saúde ou se a atmosfera geral for ofuscada pela estigmatização das doenças mentais.------------------------------------------------------------------------ABSTRACT: Saint Lucia a small island developing country with limited resources, is faced with a number of socio-economic challenges which require creative and innovative solutions to address. Combining resources across sectors to address the social, economic and environmental determinants of health has proven to be a useful strategy for improving population health in particular mental health. This study, the first of its kind for Saint Lucia sought to examine the extent to which the availability of a national mental health policy led to intersectoral action for mental health promotion and service delivery. In addition the study examined the level of intersectoral collaboration which actually exist between agencies which provide direct care and support services to people with mental illnesses and significant mental health problems. The study also aimed to identify the factors which promote or hinder intersectoral collaboration and generate recommendations which can be applied to extremely small countries with similar socio-economic profiles. Data generated from three (3) sources was synthesized to form a broad picture of the issues. An evaluation of the mental health policy of 2007, an assessment of the extent to which intersectoral action currently exist in mental health service delivery and the administration of semi-structured interviews with program managers from different agencies across sectors to identify implementation issues. The study concluded that despite the availability of a mental health policy which clearly and explicitly articulates intersectoral collaboration as a priority area for action, very little exists in the current service delivery system. Services providers across sectors acknowledge the benefits of intersectoral collaboration and that there are significant barriers to intersectoral collaboration, which in turn hinders a national approach to service planning and delivery. Intersectoral collaboration is not possible if sectors themselves are dependent on a top-down health sector driven and dominated approach, or if the general atmosphere is clouded by stigmatization of mental health illnesses.

Síntese de tetrahidroquinolinas a partir da D-eritrose

Dissertação de mestrado em Química Medicinal