Development of Asymmetric Protonation Reactions for the Synthesis of Indoline Alkaloids

Nitrogen-containing heterocycles, such as indolines and pyrroloindolines, are prevalent in a variety of diverse natural products, many of which exhibit remarkable biological activities. These frameworks have inspired innovative research aimed at discovering novel methods for their stereoselective preparation.

We have developed an enantioselective synthesis of pyrroloindolines based on a formal (3 + 2) cycloaddition of indoles and 2-amidoacrylates. This reaction is promoted by (R)-BINOL•SnCl₄; this complex is a Lewis acid-assisted Brønsted acid that effects a highly face-selective catalyst-controlled protonation of an enolate. Mechanistic studies also determined that the initial product of this reaction is an indolinium ion, which upon aqueous workup undergoes cyclization to the pyrroloindoline.

Based on this result, we investigated alternative nucleophiles to trap the indolinium ion. First, addition of sodium borohydride to the optimized reaction conditions yields indoline-containing amino acid derivatives.

Next, carbon nucleophiles were explored. Indole substrates incorporating a tethered alkene were exposed to the conditions for the formal (3 + 2) cycloaddition, resulting in a conjugate addition/asymmetric protonation/Prins cyclization cascade. In this transformation, the indolinium ion is attacked by the olefin, and the resulting carbocation is quenched by a chloride ion. Zirconium tetrachloride was found to be the optimal Lewis acid. Stoichiometric proton and chloride sources were also found to be crucial for reactivity.

Rhythms of division of some algae in situ and in laboratory culture. [Translation from: Studii Cerc.Biol.(Bot.) 21, 61-65, 1969. ]

The rhythm of division of 9 species belonging to different groups of algae were analysed in situ and in the laboratory. The research which developed in different environmental conditions attempted to establish the capacity for multiplication and assimilation of chlorophyll on the part of the algae under study with a view to placing them in a culture. The results obtained showed that the green multicellular algae (eg. Ulothrix) and the blue algae (eg. Lyngbya, Oscillatoria) are able to produce an appreciable quantity of dry matter, just as the unicellular algae. At the same time it arises that amongst the numerous factors of the environment, temperature plays one of the most important roles in the process of multiplication.

Optoelectronic quotient-selected modified signed-digit division

A novel optoelectronic quotient-selected modified signed-digit division technique is proposed. This division method generates one quotient digit per iteration involving only one shift operation, one quotient selection operation and one addition/subtraction operation. The quotient digit can be selected by observing three most significant digits of the partial remainder independent of the divisor. Two algorithms based on truth-table look-up and binary logic operations are derived. For optoelectronic implementation, an efficient shared content-addressable memory based architecture as well as compact logic array processor based architecture with an electron-trapping device is proposed. Performance evaluation of the proposed optoelectronic quotient-selected division shows that it is faster than the previously reported convergence division approach. Finally, proof-of-principle experimental results are presented to verify the effectiveness of the proposed technique. (C) 2001 Society of Photo-Optical Instrumentation Engineers.

A common axiom for classical division rules for claims problems

In this paper we introduce a new axiom, denoted claims separability, that is satisfied by several classical division rules defined for claims problems. We characterize axiomatically the entire family of division rules that satisfy this new axiom. In addition, employing claims separability, we characterize the minimal overlap rule, given by O'Neill (1982), Piniles rule and the rules in the TAL-family, introduced by Moreno-Ternero and Villar (2006), which includes the uniform gains rule, the uniform losses rule and the Talmud rule.

High-efficiency reflective diffraction gratings in fused silica as (de)multiplexers at 1.55 mu m for dense wavelength division multiplexing application

We describe high-efficiency, high-dispersion reflection gratings fabricated in bulk fused Silica illuminated by incident lights in the C + L bands as (de)multiplexers for dense wavelength division multiplexing (DWDM) application. Based on the phenomenon of total internal reflection, gratings with optimized profile parameters exhibit diffraction efficiencies of more than 90% under TM- and TE-polarized incident lights for 101-nm spectral bandwidths (1520-1620 nm) and can reach an efficiency of greater than 97% for both polarizations at a wavelength of 1550 nm. Without loss of metal absorption, without coating of dielectric film layers, and independent of tooth shape, this new kind of grating should be of great interest for DWDM application. (C) 2005 Optical Society of America.

Part I. Synchronization of the cell division cycle of HeLa cells in suspension cultures. Part II. Studies on chromosomal proteins of HeLa cells during the cell division cycle

Part I

These studies investigate the potential of single and double treatments with either 5-fluorodeoxyuridine of excess thymidine to induce cell division synchrony in suspension cultures of HeLa cells. The patterns of nucleic acid synthesis and cell proliferation have been analyzed in cultures thus synchronized. Several changes in cell population during long incubation with 5-fluorodeoxyuridine or excess thymidine are also described. These results are subjected to detailed evaluation in terms of the degree and quality of synchrony finally achieved.

Part II

Histones and non-histone proteins associated with interphase and metaphase chromosomes of HeLa cells have been qualitatively and quantitatively analyzed. Histones were fractionated by chromatography on Amberlite CG-50 and further characterized by analytical disc electrophoresis and amino acid analysis of each chromatographic fraction. It is concluded that histones of HeLa cells are comprised of only a small number of major components and that these components are homologous to those of other higher organisms. Of all the histones, arginine-rich histone III alone contains cysteine and can polymerize through formation of intermolecular disulfide bridges between histone III monomers.

A detailed comparison by chromatography and disc electrophoresis established that interphase and metaphase histones are made up of similar components. However, certain quantitative differences in proportions of different histones of interphase and metaphase cells are reported. Indirect evidence indicates that a certain proportion of metaphase histone III is polymerized through intermolecular disulfide links, whereas interphase histone III occurs mainly in the monomeric form.

Metaphase chromosomes are associated with an additional acid-soluble protein fraction which is absent from interphase chromosomes. All of these additional acid-soluble proteins of metaphase chromosomes are shown to be non-histones and it is concluded that the histone/DNA ratio is identical in interphase and metaphase chromosomes. The bulk of acid-soluble non-histone proteins of metaphase chromosomes were found to be polymerized through disulfide bridges; corresponding interphase non-histone proteins displayed no evidence of similar polymerization.

The factors responsible for the condensed configuration and metabolic inactivity of metaphase chromosomes are discussed in light of these findings.

The relationship between histone and DNA synthesis in nondividing differentiated chicken erythrocyte cells and in rapidly dividing undifferentiated HeLa cells is also investigated. Of all the histones, only arginine-rich histones are synthesized in mature erythrocytes. Histone synthesis in HeLa cells was studied in both unsynchronized and synchronized cultures. In HeLa cells, only part of the synthesis of all histone fractions is dependent on concurrent DNA synthesis, whereas all histones are synthesized in varying degrees even in the absence of DNA synthesis.

O Município na federação brasileira: limites e possibilidades de uma organização assimétrica

A federação é uma forma de Estado adotada modernamente por mais de trinta Países, e consiste numa divisão territorial do poder entre um governo central e governos locais. No Brasil, esta divisão contempla um poder local-estadual e um poder local-municipal. A federação é assimétrica quando aos entes de mesmo nível (local-estadual ou local-municipal) são atribuídos diferentes regimes jurídicos, para compensar ou equilibrar suas diversidades. O chamado federalismo fiscal estuda as receitas e despesas dos entes que integram um Estado federal. No Brasil, sempre se adotou a simetria entre os municípios. Após a análise da posição do município brasileiro na questão fiscal (receitas, encargos e formas de redistribuição de recursos), identificam-se quatro pontos passíveis de mudança normativa, para seu aperfeiçoamento: brecha vertical, guerra fiscal, critérios para criação de municípios e regiões metropolitanas. As propostas formuladas na tese são: a mudança do paradigma da simetria, instituindo-se um regime especial para os municípios com população inferior a dez mil habitantes; a proibição de que sejam criados novos municípios com este porte; novos critérios e procedimentos para criação de municípios; instituição de um conselho de municípios, junto ao Senado Federal; nova forma de rateio do fundo de participação dos municípios, com a criação do fundo de participação das regiões metropolitanas; a serem criadas pela União e geridas através de conselhos formados pelos municípios e Estados-membros participantes, na proporção de sua população, área e economia.

Prediction of Multi-Target Networks of Neuroprotective Compounds with Entropy Indices and Synthesis, Assay, and Theoretical Study of New Asymmetric 1,2-Rasagiline Carbamates

In a multi-target complex network, the links (L-ij) represent the interactions between the drug (d(i)) and the target (t(j)), characterized by different experimental measures (K-i, K-m, IC50, etc.) obtained in pharmacological assays under diverse boundary conditions (c(j)). In this work, we handle Shannon entropy measures for developing a model encompassing a multi-target network of neuroprotective/neurotoxic compounds reported in the CHEMBL database. The model predicts correctly >8300 experimental outcomes with Accuracy, Specificity, and Sensitivity above 80%-90% on training and external validation series. Indeed, the model can calculate different outcomes for >30 experimental measures in >400 different experimental protocolsin relation with >150 molecular and cellular targets on 11 different organisms (including human). Hereafter, we reported by the first time the synthesis, characterization, and experimental assays of a new series of chiral 1,2-rasagiline carbamate derivatives not reported in previous works. The experimental tests included: (1) assay in absence of neurotoxic agents; (2) in the presence of glutamate; and (3) in the presence of H2O2. Lastly, we used the new Assessing Links with Moving Averages (ALMA)-entropy model to predict possible outcomes for the new compounds in a high number of pharmacological tests not carried out experimentally.

Asymmetric conservation benefits of circle hooks in multispecies billfish recreational fisheries: a synthesis of hook performance and analysis of blue marlin (Makaira nigricans) postrelease survival

We evaluated the conservation benefits of the use of circle hooks compared with standard J hooks in the recreational fishery for Atlantic istiophorid billfishes, noting hooking location and the presence of trauma (bleeding) for 123 blue marlin (Makaira nigricans), 272 white marlin (Kajikia albida), and 132 sailfish (Istiophorus platypterus) caught on natural baits rigged with one of the two hook types. In addition, we used pop-up satellite archival tags (PSATs) to follow the fate of 61 blue marlin caught on natural baits rigged with circle hooks or on a combination of artificial lure and natural bait rigged with J hooks. The frequencies of internal hooking locations and bleeding were significantly lower with circle hooks than with J hooks for each of the three species and were significantly reduced for blue marlin caught on J hooks than for white marlin and sailfish taken on the same hook type. Analysis of the data received from 59 PSATs (two tags released prematurely) indicated no mortalities among the 29 blue marlin caught on circle hooks and two mortalities among the 30 blue marlin caught on J hooks (6.7%). Collectively, the hook location and PSAT data revealed that blue marlin, like white marlin and sailfish, derive substantial conservation benefits from the use of circle hooks, and the negative impacts of J hooks are significantly reduced for blue marlin relative to the other two species.