Photoredox generated carbonyl ylides from epoxides

Cyclic ethers, specifically, tetrahydro-, dihydro-, and furans, are pervasive and essential features in biologically active natural products and pharmaceuticals. The synthesis of cyclic ethers with atom, redox, and time economy is therefore desirable. Herein, we describe studies that led to the conception and development of photoredox methodologies that are able to catalytically generate carbonyl ylides from epoxides. These can be engaged in [3+2] dipolar cycloadditions with dipolarophiles to afford densely functionalized cyclic ethers in a sole, redox-neutral chemical operation. The invention of this technology hinged on the discovery of two unique photoredox catalysts that, in parallel, are able to mitigate the emerging challenges of generating electronically diverse carbonyl ylides. Empirical and theoretical studies of this reaction ultimately led to the proposal and validation of a general paradigm that can be used to assert a priori whether carbonyl ylide formation is possible from an epoxide. Lastly, the application of this methodology to a bioinspired, unified synthesis of the classical lignan family of natural products is described. This chemistry was accomplished by intercepting Nature’s route at a pivotal intermediate, which served as a nodal scaffold for the synthesis of all eight members found within classical lignans

Análisis de pre inversión en importación e instalación de equipos de fotocopiado remanufacturados en el centro del país

Se muestra un estudio de la posibilidad de transporte y la instalación de equipos de fotocopiado con mejoras en su funcionamiento. Se presenta un análisis que incluye el estudio del perfil del proyecto, su pre factibilidad y factibilidad de acuerdo al análisis de entorno del contexto de la zona de trabajo propuesta en la implantación. La alternativa de solución se escoge de acuerdo a la viabilidad de la evaluación económica, financiera, comercial, ambiental, política y social, concluyéndose que la factibilidad está condicionada por los procesos de importación hacia el territorio nacional de equipos y ello restringe de gran manera la posibilidad de invertir en el proyecto

Improving reading skills in beginner learners by means of graphic organizers and the use of english-leveled readers

100 Páginas.La comprensión lectora juega un papel importante en el aprendizaje de una lengua. investigaciones previas han descubierto que, para lograr una lectura efectiva, es necesario que los estudiantes mejoren su comprensión. Sin embargo, se les ha prestado poca atención a las ayudas de organización gráfica y al uso de libros de lectura nivelados en inglés para apoyar el proceso de lectura. En este estudio, enmarcado en una investigación acción cualitativa, se utilizaron evaluaciones, planes de clase, diarios del profesor y encuestas con el fin de recolectar información acerca del impacto de los organizadores gráficos en la comprensión lectora de los estudiantes de segundo grado. La información fue analizada utilizando el enfoque de teoría fundamentada. En los resultados, los estudiantes dieron cuenta de la capacidad para entender textos nivelados y elaborar reportes de manera adecuada. Esto demostró que los organizadores gráficos son una estrategia efectiva para mejorar la comprensión lectora en los estudiantes. Esto teniendo en cuenta la etapa del pensamiento de los niños y toda la contribución de las ayudas visuales al proceso de aprendizaje de una lengua extranjer

Propuesta curricular para la integración del ingles al área de Ciencias Naturales

El proyecto de investigación se desarrolló en el Instituto Técnico Industrial Francisco José de Caldas, el cual desarrolla un proceso de bilingüismo donde se propone, entre otras cosas, la enseñanza del área de ciencias naturales en inglés. El plantel educativo cuenta con un currículo monolingüe. No obstante, el grupo investigador evidenció la necesidad de diseñar una propuesta curricular para integrar el inglés al área de ciencias naturales con el fin de optimizar el proceso bilingüe del colegioThe research project was developed in the Francisco José de Caldas Industrial Technical Institute, which develops a process of bilingualism which aims, among other things, teaching the area of natural science in English. The campus has a monolingual curriculum. However, the research team demonstrated the need to design a curriculum to integrate the English to the area of natural sciences in order to optimize the bilingual college proces

One-pot synthesis of epoxides from benzyl alcohols and aldehydes

A one-pot synthesis of epoxides from commercially available benzyl alcohols and aldehydes is described. The reaction proceeds through in situ generation of sulfonium salts from benzyl alcohols and their subsequent deprotonation for use in Corey–Chaykovsky epoxidation of aldehydes. The generality of the method is exemplified by the synthesis of 34 epoxides that were made from an array of electronically and sterically varied alcohols and aldehydes

Redesign of a Pyrylium Photoredox Catalyst and Its Application to the Generation of Carbonyl Ylides

We report the exploration into photoredox generation of carbonyl ylides from benzylic epoxides using newly designed 4-mesityl-2,6-diphenylpyrylium tetrafluoroborate (MDPT) and 4-mesityl-2,6-di-<i>p</i>-tolylpyrylium tetrafluoroborate (MD­(<i>p</i>-tolyl)­PT) catalysts. These catalysts are excited at visible wavelengths, are highly robust, and exhibit some of the highest oxidation potentials reported. Their utility was demonstrated in the mild and efficient generation of carbonyl ylides from benzylic epoxides that otherwise could not be carried out by current common photoredox catalysts

Chemodivergent C(sp3)–H and C(sp2)–H Cyanomethylation Using Engineered Carbene Transferases

The ubiquity of C–H bonds presents an attractive opportunity to elaborate and build complexity in organic molecules. Methods for selective functionalization, however, often must differentiate among multiple chemically similar and, in some cases indistinguishable, C–H bonds within the same molecule. An advantage of enzymes is that they can be finely tuned using directed evolution to achieve control over divergent C–H functionalization pathways. Here, we present engineered enzymes that effect a new-to-nature C–H alkylation (C–H carbene insertion) with unparalleled selectivity: two complementary carbene C–H transferases derived from a cytochrome P450 from Bacillus megaterium deliver an α-cyanocarbene into the α-amino C(sp3)–H bonds or the ortho-arene C(sp2)–H bonds of N-substituted arenes. These two transformations proceed via different mechanisms, yet only minimal changes to the protein scaffold (nine mutations, less than 2% of the sequence) were needed to adjust the enzyme’s control over the site-selectivity of cyanomethylation. The X-ray crystal structure of the selective C(sp3)–H alkylase, P411-PFA, reveals an unprecedented helical disruption which alters the shape and electrostatics in the enzyme active site. Overall, this work demonstrates the advantages of using enzymes as C–H functionalization catalysts for divergent molecular derivatization

Enzymatic Nitrogen Insertion into Unactivated C–H Bonds

Selective functionalization of aliphatic C–H bonds, ubiquitous in molecular structures, could allow ready access to diverse chemical products. While enzymatic oxygenation of C–H bonds is well established, the analogous enzymatic nitrogen functionalization is still unknown; nature is reliant on pre-oxidized compounds for nitrogen incorporation. Likewise, synthetic methods for selective nitrogen derivatization of unbiased C–H bonds remain elusive. In this work, new-to-nature heme-containing nitrene transferases were used as starting points for the directed evolution of enzymes to selectively aminate and amidate unactivated C(sp3)–H sites. The desymmetrization of methyl- and ethylcyclohexane with divergent site selectivity is offered as demonstration. The evolved enzymes in these lineages are highly promiscuous and show activity towards a wide array of substrates, providing a foundation for further evolution of nitrene transferase function. Computational studies and kinetic isotope effects (KIEs) are consistent with a stepwise radical pathway involving an irreversible, enantiodetermining hydrogen atom transfer (HAT), followed by a lower-barrier diastereoselectivity determining radical rebound step. In-enzyme molecular dynamics (MD) simulations reveal a predominantly hydrophobic pocket with favorable dispersion interactions with the substrate. By offering a direct path from saturated precursors, these enzymes present a new biochemical logic for accessing nitrogen-containing compounds

Defects in immune response to Toxoplasma gondii are associated with enhanced HIV-1-related neurocognitive impairment in co-infected patients.

Human immunodeficiency virus-1 (HIV-1) and Toxoplasma gondii can invade the central nervous system and affect its functionality. Advanced HIV-1 infection has been associated with defects in immune response to T. gondii, leading to reactivation of latent infections and development of toxoplasmic encephalitis. This study evaluates relationship between changes in immune response to T. gondii and neurocognitive impairment in HIV-1/T. gondii co-infected patients, across different stages of HIV-1 infection. The study assessed the immune response to T. gondii by measuring cytokine production in response to parasite antigens, and also neurocognitive functions by performing auditory and visual P300 cognitive evoked potentials, short term memory (Sternberg) and executive function tasks (Wisconsin Card Sorting Test-WCST) in 4 groups of individuals: HIV-1/T. gondii co-infected (P2), HIV-1-infected/T. gondii-non-infected (P1), HIV-1-non-infected/T. gondii-infected (C2) and HIV-1-non-infected/T. gondii-non-infected (C1). Patients (P1 and P2) were grouped in early/asymptomatic (P1A and P2A) or late/symptomatic (P1B/C and P2B/C) according to peripheral blood CD4+ T lymphocyte counts (>350 or <350/μL, respectively). Groups were compared using T-student or U-Mann-Whitney tests as appropriate, p<0.05 was considered as significantly. For P300 waves, HIV-1-infected patients (P1) had significantly longer latencies and significantly smaller amplitudes than uninfected controls, but HIV-1/T. gondii co-infected patients (P2) had significantly longer latencies and smaller amplitude than P1. P1 patients had significantly poorer results than uninfected controls in Sternberg and WCST, but P2 had significantly worse results than P1. HIV-1 infection was associated with significantly lower production of IL-2, TNF-α and IFN-γ in response to T. gondii from early/asymptomatic stages, when comparing P2 patients to C2 controls. These findings may indicate impairment in anti-parasitic response in co-infected patients, facilitating early limited reactivation of the parasitic latent infection, therefore creating cumulative damage in the brain and affecting neurocognitive functions from asymptomatic stages of HIV-1 infection, as suggested by defects in co-infected patients in this study