10 research outputs found
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鈥檚 route at a pivotal intermediate, which served as a nodal scaffold for the synthesis of all eight members found within classical lignans
An谩lisis de pre inversi贸n en importaci贸n e instalaci贸n de equipos de fotocopiado remanufacturados en el centro del pa铆s
Se muestra un estudio de la posibilidad de transporte y la instalaci贸n de equipos de fotocopiado con mejoras en su funcionamiento. Se presenta un an谩lisis que incluye el estudio del perfil del proyecto, su pre factibilidad y factibilidad de acuerdo al an谩lisis de entorno del contexto de la zona de trabajo propuesta en la implantaci贸n. La alternativa de soluci贸n se escoge de acuerdo a la viabilidad de la evaluaci贸n econ贸mica, financiera, comercial, ambiental, pol铆tica y social, concluy茅ndose que la factibilidad est谩 condicionada por los procesos de importaci贸n 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 P谩ginas.La comprensi贸n 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 comprensi贸n. Sin embargo, se les ha prestado poca atenci贸n a las ayudas de organizaci贸n gr谩fica y al uso de libros de lectura nivelados en ingl茅s para apoyar el proceso de lectura. En este estudio, enmarcado en una investigaci贸n acci贸n cualitativa, se utilizaron evaluaciones, planes de clase, diarios del profesor y encuestas con el fin de recolectar informaci贸n acerca del impacto de los organizadores gr谩ficos en la comprensi贸n lectora de los estudiantes de segundo grado. La informaci贸n fue analizada utilizando el enfoque de teor铆a fundamentada. En los resultados, los estudiantes dieron cuenta de la capacidad para entender textos nivelados y elaborar reportes de manera adecuada. Esto demostr贸 que los organizadores gr谩ficos son una estrategia efectiva para mejorar la comprensi贸n lectora en los estudiantes. Esto teniendo en cuenta la etapa del pensamiento de los ni帽os y toda la contribuci贸n de las ayudas visuales al proceso de aprendizaje de una lengua extranjer
Propuesta curricular para la integraci贸n del ingles al 谩rea de Ciencias Naturales
El proyecto de investigaci贸n se desarroll贸 en el Instituto T茅cnico Industrial Francisco Jos茅 de Caldas, el cual desarrolla un proceso de biling眉ismo donde se propone, entre otras cosas, la ense帽anza del 谩rea de ciencias naturales en ingl茅s. El plantel educativo cuenta con un curr铆culo monoling眉e. No obstante, el grupo investigador evidenci贸 la necesidad de dise帽ar una propuesta curricular para integrar el ingl茅s al 谩rea de ciencias naturales con el fin de optimizar el proceso biling眉e del colegioThe research project was developed in the Francisco Jos茅 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鈥揅haykovsky 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颅(<i>p</i>-tolyl)颅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
Photoredox Generated Carbonyl Ylides Enable a Modular Approach to Aryltetralin, Dihydronaphthalene, and Arylnaphthalene Lignans
Chemodivergent C(sp3)鈥揌 and C(sp2)鈥揌 Cyanomethylation Using Engineered Carbene Transferases
The ubiquity of C鈥揌 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鈥揌 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鈥揌 functionalization pathways. Here, we present engineered enzymes that effect a new-to-nature C鈥揌 alkylation (C鈥揌 carbene insertion) with unparalleled selectivity: two complementary carbene C鈥揌 transferases derived from a cytochrome P450 from Bacillus megaterium deliver an 伪-cyanocarbene into the 伪-amino C(sp3)鈥揌 bonds or the ortho-arene C(sp2)鈥揌 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鈥檚 control over the site-selectivity of cyanomethylation. The X-ray crystal structure of the selective C(sp3)鈥揌 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鈥揌 functionalization catalysts for divergent molecular derivatization
Enzymatic Nitrogen Insertion into Unactivated C鈥揌 Bonds
Selective functionalization of aliphatic C鈥揌 bonds, ubiquitous in molecular structures, could allow ready access to diverse chemical products. While enzymatic oxygenation of C鈥揌 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鈥揌 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)鈥揌 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/渭L, 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-伪 and IFN-纬 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