Strategies for the Stereoselective Synthesis of Carbon Quaternary Centers via Transition Metal-Catalyzed Alkylation of Enolate Compounds

Notwithstanding advances in modern chemical methods, the selective installation of sterically encumbered carbon stereocenters, in particular all-carbon quaternary centers, remains an unsolved problem in organic chemistry. The prevalence of all-carbon quaternary centers in biologically active natural products and pharmaceutical compounds provides a strong impetus to address current limitations in the state of the art of their generation. This thesis presents four related projects, all of which share in the goal of constructing highly-congested carbon centers in a stereoselective manner, and in the use of transition-metal catalyzed alkylation as a means to address that goal.

The first research described is an extension of allylic alkylation methodology previously developed in the Stoltz group to small, strained rings. This research constitutes the first transition metal-catalyzed enantioselective α-alkylation of cyclobutanones. Under Pd-catalysis, this chemistry affords all–carbon α-quaternary cyclobutanones in good to excellent yields and enantioselectivities.

Next is described our development of a (trimethylsilyl)ethyl β-ketoester class of enolate precursors, and their application in palladium–catalyzed asymmetric allylic alkylation to yield a variety of α-quaternary ketones and lactams. Independent coupling partner synthesis engenders enhanced allyl substrate scope relative to allyl β-ketoester substrates; highly functionalized α-quaternary ketones generated by the union of our fluoride-triggered β-ketoesters and sensitive allylic alkylation coupling partners serve to demonstrate the utility of this method for complex fragment coupling.

Lastly, our development of an Ir-catalyzed asymmetric allylic alkylation of cyclic β-ketoesters to afford highly congested, vicinal stereocenters comprised of tertiary and all-carbon quaternary centers with outstanding regio-, diastereo-, and enantiocontrol is detailed. Implementation of a subsequent Pd-catalyzed alkylation affords dialkylated products with pinpoint stereochemical control of both chiral centers. The chemistry is then extended to include acyclic β-ketoesters and similar levels of selective and functional group tolerance are observed. Critical to the successful development of this method was the employment of iridium catalysis in concert with N-aryl-phosphoramidite ligands.

Phi 140 mm sapphire crystal growth by temperature gradient techniques and its color centers

Sapphire crystals, 140 mm in diameter and 90 turn in height, have been grown by temperature gradient techniques (TGT). The growth direction of the boule was fixed by means of Lane X-ray diffraction. A prominent 204 nm absorption band in TGT-Al2O3. which does not appear in single crystals grown by Czochralski method has been studied. Analysis further substantiates the F-center model of this band. Two relatively weaker bands absorbing at 232 nm and 254 nm were ascribed to F+ centers. F-type centers concentration was determined using Smakula's equation. (c) 2005 Elsevier B.V. All rights reserved.

Color centers and charge state change in Ce : YAG crystals grown by temperature gradient techniques

Color centers and impurity defects of Ce:YAG crystals grown in reduction atmosphere by temperature gradient techniques have been investigated by means of gamma irradiation and thermal treatments. Four absorption bands associated with color centers or impurity defects at 235, 255, 294 and 370 nm were observed in as-grown crystals. Changes in optical intensity of the 235 and 370 nm bands after gamma irradiation indicate that they are associated with F+-type color center. Charge state change processes of Fe3+ impurity and Ce3+ ions take place in the irradiation process. The variations of Ce3+ ions concentration clearly indicate that Ce4+ ions exist in Ce:YAG crystals and gamma irradiations could increase the concentration of Ce3+ ions. Annealing treatments and the changes in optical density suggest that a heterovalent impurity ion associated with the 294 nm band seems to be present in the crystals. (c) 2005 Elsevier B.V. All rights reserved.

Color centers and charge state recharge in gamma-irradiated Yb : YAP

Gamma-ray irradiation induced color centers and charge state recharge of impurity and doped ion in 10 at.% Yb:YAP have been studied. The change in the additional absorption (AA) spectra is mainly related to the charge exchange of the impurity Fe2+, Fe3+ and Yb3+ ions. Two impurity color center bands at 255 and 313 nm were attributed to Fe3+ and Fe2+ ions, respectively. The broad AA band centered at 385 nm may be associated with the cation vacancies and F-type center. The transition Yb3+ -> Yb2+ takes place in the process of gamma-irradiation. Oxygen annealing and gamma-ray irradiation lead to an opposite effect on the absorption properties of the Yb:YAP crystal. In the air annealing process, the transition Fe2+ -> Fe3+ and Yb2+ -> Yb3+ take place and the color centers responsible for the 385 nm band was destroyed. (c) 2005 Elsevier B.V. All rights reserved.

Color centers in Yb : YAG crystals grown by temperature-gradient techniques

Yb: YAG (Yb: Y3Al5O12) crystals have been grown by temperature-gradient techniques (TGT) and their color centers and impurity defects were investigated by means of gamma irradiations and thermal treatment. Two color centers located at 255 and 290 nm were observed in the as-grown TGT-Yb: YAG. Analysis shows that the 255 nm band may be associated with Fe3+ ions. Absorption intensity changes of the 290 nm band after gamma irradiation and thermal treatment indicate that this band may be associated with oxygen-vacancy defects. (c) 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The labour market in the Basque Country: University Employment Centers

This project is a study of the Labour Market in the Basque Country. First of all, we have analysed the position of the Basque Country in the European Union employment situation by gender and age. Secondly, we have studied the educational level of the Basque Country from the European Union perspective. Thirdly, we have showed the importance of labour orientation in educational level, especially in higher education. Finally, the design of new employment policies to promote the creation of jobs and stability of the labour market depends on: new industries and university employment policies.

Sociologia do trauma: elementos sociogenéticos e psicogenéticos

O presente trabalho investiga os diferentes processos sociais relacionados ao surgimento do transtorno de estresse pós-traumático (TEPT) no contexto brasileiro. Categoria diagnóstica norte-americana instituída na década de 1980 pela terceira edição do Manual Diagnóstico e Estatístico de Transtornos Mentais (Diagnostic and Statistical Manual of Mental Disorders DSM-III) uma publicação da Associação Americana de Psiquiatria (American Psychiatric Association APA) o TEPT tornou-se, desde a sua aparição, uma das categorias nosológicas mais difundidas, estudadas e diagnosticadas da psiquiatria contemporânea. A partir do cotidiano de um laboratório de pesquisa e tratamento do TEPT, de análises conversacionais dos atendimentos médicos, de um estudo das diferentes escalas psiquiátricas utilizadas no acompanhamento dos pacientes e de pesquisas sobre a mídia relacionada às experiências traumáticas buscou-se entender os entrelaçamentos entre os processos de difusão e a construção da legitimidade da categoria diagnóstica do TEPT. A abordagem aqui proposta pretende ir além do aparente dilema entre uma concepção medicalizada que assumem a existência o TEPT como um fenômeno natural e as abordagens sócio-antropológicas que veem o TEPT como uma experiência culturalmente construída. Por fim, pretendo mostrar, pela investigação dos alicerces políticos e culturais dos denominados transtornos mentais, que o estatuto social dos diagnósticos e dos tratamentos da moderna psiquiatria só pode ser compreendido tendo como referência as dinâmicas de longo prazo nas sociedades contemporâneas.

The U.S. Gulf of Mexico Party Boat Industry: Activity Centers, Species Targeted, and Fisheries Management Opinions

In addition to providing an overview of the party boat fishery in the U.S. Gulf of Mexico, a management-oriented methodology is presented that can be used elsewhere to assess regulatory impacts. Party boat operators were interviewed to determine species targeted, percent time committed to targeting each species, and opinions on current catch restrictions. Over two-thirds of the fieet was located on the west coast of Florida. Overall, most boats targeted <5 species. Four species accounted for 90 percent of the estimated effort by party boats in the U.S. Gulf of Mexico: Snapper; Lutjanus sp.; grouper, Epinephelus sp. and Mycteroperca sp.; amberjack, Seriola dumerili; and king mackerel, Scomberomorus cavalla. Party boat effort in Texas was devoted primarily to snapper, whereas in Florida most effort was devoted to snapper and grouper collectively. Party boat operators were diverse in their opinions of management regulations in force when interviewed. Results revealed why major opposition would he expected from Texas party boat operators for red snapper bag limits and other restrictions proposed by the Gulf of Mexico Fishery Management Council.

The U.S. Gulf of Mexico Charter Boat Industry: Activity Centers, Species Targeted, and Fisheries Management Opinions

The charter boat industry in U. S. Gulf of Mexico provides access to offshore fishing opportunities for about 570,000 passengers per year on 971 boats. A 25% random sample of charter boat operators was interviewed during 1987-88 to determine species targeted, percent time committed to targeting each species, and reactions to existing catch restrictions. Three-fourths of the charter boat fleet was in Florida, 13% in Texas, 5% in Louisiana, 4% in Alabama, and 2% in Mississippi. Responses were diverse regarding species focus within the region. Species of dominant importance included groupers, Epinephelus sp. and Mycteroperca sp. (Fla.); snapper, Lutjanus campechanus (Ala., Fla., Miss., and La.); king mackerel, Scomberomorus cavalla (Miss., Tex., Ala. and Fla.); spotted seatrout, Cynoscion nebulosus (Tex. and La.); and red drum, Sciaenops ocellatus (Tex. and La). Catch restrictions were generally supported with higher levels of opposition to restricted high effort fish and/or one fish or closed fishery limits.

Frequência cardíaca peritraumática após exposição ao trauma como preditor de transtorno de estresse pós-traumático em adultos: revisão sistemática e metanálise.

O transtorno de estresse pós-traumático (TEPT) é um transtorno de ansiedade que pode ser desenvolvido após a ocorrência de um evento traumático, e que costuma vir acompanhado de um significativo comprometimento da qualidade de vida. Indivíduos diagnosticados com o TEPT apresentam níveis de frequência cardíaca mais elevados em situações de exposição a eventos estressores, como sons e imagens que relembram a experiência traumática. No entanto, estudos que avaliaram a frequência cardíaca no momento do trauma como preditor do desenvolvimento de TEPT não apresentam resultados consistentes. Os objetivos deste trabalho foram: verificar se frequência cardíaca (FC) peritraumática de repouso, após exposição ao trauma, é um fator preditor para o desenvolvimento do TEPT e para a gravidade dos sintomas de TEPT em adultos. Foi realizada uma revisão sistemática, seguida de metanálise, utilizando-se as bases eletrônicas PUBMED, LILACS, PILOTS, PsycoINFO e Web of Science. Foram incluídos 17 estudos nesta revisão sistemática. Os resultados de dez estudos foram utilizados para a metanálise das diferenças de médias de FC combinada. Oito estudos foram utilizados para a metanálise das correlações entre a FC e a gravidade dos sintomas de TEPT. Modelos de meta-regressão foram ajustados para identificar variáveis que pudessem explicar a heterogeneidade entre os estudos. A FC peritraumática no grupo de pacientes com TEPT é, em média, 3,98 batimento por mimuto (bpm) (p=0,04) maior em comparação com aqueles sem o transtorno, e o coeficiente de correlação de Pearson combinado foi de 0,14 (p=0,05).Consistente com a hipótese levantada, a frequência cardíaca peritraumática de repouso foi maior em indivíduos que desenvolveram o TEPT. Contudo, mensuração mais próxima do evento traumático e a exclusão de casos dissociativos poderão ampliar a magnitude do efeito encontrado, tornando este biomarcador simples e facilmente obtido um preditor clinicamente útil do desenvolvimento de TEPT.

National Centers for Coastal Ocean Science Coastal Ecosystem Assessment Program: a manual of methods

Environmental managers strive to preserve natural resources for future generations but have limited decision-making tools to define ecosystem health. Many programs offer relevant broad-scale, environmental policy information on regional ecosystem health. These programs provide evidence of environmental condition and change, but lack connections between local impacts and direct effects on living resources. To address this need, the National Oceanic and Atmospheric Administration/National Ocean Service (NOAA/NOS) Cooperative Oxford Laboratory (COL), in cooperation with federal, state, and academic partners, implemented an integrated biotic ecosystem assessment on a sub-watershed 14-digit Hydrologic Unit Code (HUD) scale in Chesapeake Bay. The goals of this effort were to 1) establish a suite of bioindicators that are sensitive to ecosystem change, 2) establish the effects of varying land-use patterns on water quality and the subsequent health of living resources, 3) communicate these findings to local decision-makers, and 4) evaluate the success of management decisions in these systems. To establish indicators, three sub-watersheds were chosen based on statistical analysis of land-use patterns to represent a gradient from developed to agricultural. The Magothy (developed), Corsica (agricultural), and Rhode (reference) Rivers were identified. A random stratified design was developed based on depth (2m contour) and river mile. Sampling approaches were coordinated within this structure to allow for robust system comparisons. The sampling approach was hierarchal, with metrics chosen to represent a range from community to cellular level responses across multiple organisms. This approach allowed for the identification of sub-lethal stressors, and assessment of their impact on the organism and subsequently the population. Fish, crabs, clams, oysters, benthic organisms, and bacteria were targeted, as each occupies a separate ecological niche and may respond dissimilarly to environmental stressors. Particular attention was focused on the use of pathobiology as a tool for assessing environmental condition. By integrating the biotic component with water quality, sediment indices, and land- use information, this holistic evaluation of ecosystem health will provide management entities with information needed to inform local decision-making processes and establish benchmarks for future restoration efforts.

Saline-saturated DMSO-EDTA as a storage medium for microbial DNA analysis from coral mucus swab samples

The mucus surface layer of corals plays a number of integral roles in their overall health and fitness. This mucopolysaccharide coating serves as vehicle to capture food, a protective barrier against physical invasions and trauma, and serves as a medium to host a community of microorganisms distinct from the surrounding seawater. In healthy corals the associated microbial communities are known to provide antibiotics that contribute to the coral’s innate immunity and function metabolic activities such as biogeochemical cycling. Culture-dependent (Ducklow and Mitchell, 1979; Ritchie, 2006) and culture-independent methods (Rohwer, et al., 2001; Rohwer et al., 2002; Sekar et al., 2006; Hansson et al., 2009; Kellogg et al., 2009) have shown that coral mucus-associated microbial communities can change with changes in the environment and health condition of the coral. These changes may suggest that changes in the microbial associates not only reflect health status but also may assist corals in acclimating to changing environmental conditions. With the increasing availability of molecular biology tools, culture-independent methods are being used more frequently for evaluating the health of the animal host. Although culture-independent methods are able to provide more in-depth insights into the constituents of the coral surface mucus layer’s microbial community, their reliability and reproducibility rely on the initial sample collection maintaining sample integrity. In general, a sample of mucus is collected from a coral colony, either by sterile syringe or swab method (Woodley, et al., 2008), and immediately placed in a cryovial. In the case of a syringe sample, the mucus is decanted into the cryovial and the sealed tube is immediately flash-frozen in a liquid nitrogen vapor shipper (a.k.a., dry shipper). Swabs with mucus are placed in a cryovial, and the end of the swab is broken off before sealing and placing the vial in the dry shipper. The samples are then sent to a laboratory for analysis. After the initial collection and preservation of the sample, the duration of the sample voyage to a recipient laboratory is often another critical part of the sampling process, as unanticipated delays may exceed the length of time a dry shipper can remain cold, or mishandling of the shipper can cause it to exhaust prematurely. In remote areas, service by international shipping companies may be non-existent, which requires the use of an alternative preservation medium. Other methods for preserving environmental samples for microbial DNA analysis include drying on various matrices (DNA cards, swabs), or placing samples in liquid preservatives (e.g., chloroform/phenol/isoamyl alcohol, TRIzol reagent, ethanol). These methodologies eliminate the need for cold storage, however, they add expense and permitting requirements for hazardous liquid components, and the retrieval of intact microbial DNA often can be inconsistent (Dawson, et al., 1998; Rissanen et al., 2010). A method to preserve coral mucus samples without cold storage or use of hazardous solvents, while maintaining microbial DNA integrity, would be an invaluable tool for coral biologists, especially those in remote areas. Saline-saturated dimethylsulfoxide-ethylenediaminetetraacetic acid (20% DMSO-0.25M EDTA, pH 8.0), or SSDE, is a solution that has been reported to be a means of storing tissue of marine invertebrates at ambient temperatures without significant loss of nucleic acid integrity (Dawson et al., 1998, Concepcion et al., 2007). While this methodology would be a facile and inexpensive way to transport coral tissue samples, it is unclear whether the coral microbiota DNA would be adversely affected by this storage medium either by degradation of the DNA, or a bias in the DNA recovered during the extraction process created by variations in extraction efficiencies among the various community members. Tests to determine the efficacy of SSDE as an ambient temperature storage medium for coral mucus samples are presented here.