Gold Catalysis: Recent Developments and Future Trends

The field of homogeneous gold catalysis has developed exponentially over the past ten years. Even if the array of gold-mediated transformations is extremely broad, a common feature stems from the ability of gold to activate unsaturated moieties due to the strong relativistic effects governing its coordination behavior. Starting with a short historical perspective, this review compiles the recent advances in two fundamental areas: first, the rearrangement of propargylic carboxylates and second, ring-expansion processes, both topics of interest in our research group at the Organic Chemistry Institute of the University of Zurich

Dual Nickel/Photoredox-Catalyzed Asymmetric Carbosulfonylation of Alkenes

An asymmetricthree-componentcarbosulfonylationof alkenesis presentedhere. The reaction,involvingthesimultaneousformationof a C−C and a C−S bond acrosstheπ-system,uses a dual nickel/photoredoxcatalyticsystemto producebothβ-aryl andβ-alkenylsulfonesin high yields and with excellentlevels of stereocontrol(up to 99:1 er). This protocolexhibitsabroadsubstratescope and excellentfunctionalgrouptoleranceand its syntheticpotentialhas been demonstratedby successfulapplicationstowardpharmacologicallyrelevantmolecules.A broadarray of controlexperimentssupportsthe involvementof asecondaryalkyl radicalintermediategeneratedthroughradicaladditionof a sulfonylradicalto the doublebond.Moreover,stoichiometricand cross-overexperimentsfurthersuggestan underlyingNi(0)/Ni(I)/Ni(III)pathwayoperativein thesetransformations

Chelation-assisted C–C bond activation of biphenylene by gold(<scp>i</scp>) halides

A chelation-assisted oxidative addition of gold(i) into the C-C bond of biphenylene is reported here. The presence of a coordinating group (pyridine, phosphine) in the biphenylene unit enabled the use of readily available gold(i) halide precursors providing a new, straightforward entry towards cyclometalated (N^C^C)- and (P^C)-gold(iii) complexes. Our study, combining spectroscopic and crystallographic data with DFT calculations, showcases the importance of neighboring, weakly coordinating groups towards the successful activation of strained C-C bonds by gold

Asociación entre la enfermedad periodontal y el hábito tabáquico en los pacientes atendidos en la clínica estomatológica de la Universidad Inca Garcilaso de la Vega durante el año 2018

Introducción: La enfermedad periodontal se le denomina a una serie de procesos patológicos de carácter infeccioso que tiene en común afectar los tejidos de soporte del diente. Métodos: Se realizó una prueba piloto en 100 pacientes de ambos sexos , siendo pacientes atendidos en la clínica de la Universidad Inca Garcilaso de la Vega.Introduction: The disease periodontal are you called to a series of processes pathological of character infectious that has in common affect them woven of support of the tooth. Methods: Is carried out a test pilot in 100 patients of both sexes of different range of age, being patients attended in the clinical of the University Inca Garcilaso of the Vega

Kinase selectivity potential for inhibitors targeting the ATP binding site: a network analysis

Motivation and method: Small-molecule inhibitors targeting the adenosine triphosphate (ATP) binding pocket of the catalytic domain of protein kinases have potential to become drugs devoid of (major) side effects, particularly if they bind selectively. Here, the sequences of the 518 human kinases are first mapped onto the structural alignment of 116 kinases of known three-dimensional structure. The multiple structure alignment is then used to encode the known strategies for developing selective inhibitors into a fingerprint. Finally, a network analysis is used to partition the kinases into clusters according to similarity of their fingerprints, i.e. physico-chemical characteristics of the residues responsible for selective binding. Results: For each kinase the network analysis reveals the likelihood to find selective inhibitors targeting the ATP binding site. Systematic guidelines are proposed to develop selective inhibitors. Importantly, the network analysis suggests that the tyrosine kinase EphB4 has high selectivity potential, which is consistent with the selectivity profile of two novel EphB4 inhibitors. Contact: [email protected]; [email protected] Supplementary information: Supplementary data are available at Bioinformatics onlin

Nickel-Catalyzed Enantioselective Electrochemical Reductive Cross-Coupling of Aryl Aziridines with Alkenyl Bromides

An electrochemically driven nickel-catalyzed enantioselective reductive cross-coupling of aryl aziridines with alkenyl bromides has been developed, affording enantioenriched β-aryl homoallylic amines with excellent E-selectivity. This electroreductive strategy proceeds in the absence of heterogeneous metal reductants and sacrificial anodes by employing constant current electrolysis in an undivided cell with triethylamine as a terminal reductant. The reaction features mild conditions, remarkable stereocontrol, broad substrate scope, and excellent functional group compatibility, which was illustrated by the late-stage functionalization of bioactive molecules. Mechanistic studies indicate that this transformation conforms with a stereoconvergent mechanism in which the aziridine is activated through a nucleophilic halide ring-opening process

Oxidant speciation and anionic ligand effects in the gold-catalyzed oxidative coupling of arenes and alkynes

The mechanism of the gold-catalyzed oxidative cross-coupling of arenes and alkynes has been studied in detail combining stoichiometric experiments with putative reaction intermediates and DFT calculations. Our data suggest that ligand exchange between the alkyne, the Au(I)-catalyst and the hypervalent iodine reagent is responsible for the formation of both, a Au(I)-acetylide complex as well as a more reactive “non-symmetric” I(III) oxidant, responsible for the crucial Au(I)/Au(III) turnover. Further, the reactivity of the in situ generated Au(III)-acetylide complex is governed by the nature of the anionic ligands transferred by the I(III) oxidant: while halogen ligands remain unreactive, acetato ligands are efficiently displaced by the arene to yield the observed Csp2-Csp cross-coupling products through an irreversible reductive elimination step. Finally, the nature of competitive processes and catalyst deactivation pathways has also been unraveled. This detailed investigation provides insights not only on the specific features of the species involved in oxidative gold-catalyzed cross couplings but also highlights the importance of both ancillary and anionic ligands on the reactivity of the key Au(III) intermediates

PTP1B deficiency increases glucose uptake in neonatal hepatocytes: involvement of IRA/GLUT2 complexes

11 pages, 5 figures, 1 table.The contribution of the liver to glucose utilization is essential to maintain glucose homeostasis. Previous data from protein tyrosine phosphatase (PTP) 1B-deficient mice demonstrated that the liver is a major site for PTP1B action in the periphery. In this study, we have investigated the consequences of PTP1B deficiency in glucose uptake in hepatocytes from neonatal and adult mice. The lack of PTP1B increased basal glucose uptake in hepatocytes from neonatal (3-5 days old) but not adult (10-12 wk old) mice. This occurs without changes in hexokinase, glucokinase, and glucose 6-phosphatase enzymatic activities. By contrast, the glucose transporter GLUT2 was upregulated at the protein level in neonatal hepatocytes and livers from PTP1B-deficient neonates. These results were accompanied by a significant increase in the net free intrahepatic glucose levels in the livers of PTP1B(-/-) neonates. The association between GLUT2 and insulin receptor (IR) A isoform was increased in PTP1B(-/-) neonatal hepatocytes compared with the wild-type. Indeed, PTP1B deficiency in neonatal hepatocytes shifted the ratio of isoforms A and B of the IR by increasing the amount of IRA and decreasing IRB. Moreover, overexpression of IRA in PTP1B(-/-) neonatal hepatocytes increased the amount of IRA/GLUT2 complexes. Conversely, hepatocytes from adult mice only expressed IRB. Since IRA plays a direct role in the regulation of glucose uptake in neonatal hepatocytes through its specific association with GLUT2, we propose the increase in IRA/GLUT2 complexes due to PTP1B deficiency as the molecular mechanism of the increased glucose uptake in the neonatal stage.This work was supported by grants BFU2005-1615 (A. M. Valverde), SAF 2004-5545 (M. Benito), and CIBER de Diabetes y Enfermedades Metabólicas Asociadas (ISCIII, Spain). A. González-Rodríguez and C. Nevado were recipients of fellowships from Ministerio de Educación y Ciencia (Spain).Peer reviewe

[C^N]‐Alkenyl Gold(III) Complexes by Proximal Ring‐Opening of (2‐Pyridyl)alkylidenecyclopropanes: Mechanistic Insights

This is the peer reviewed version of the following article: J. A. González, F. Verdugo, J. L. Mascareñas, F. López, C. Nevado, Angew. Chem. Int. Ed. 2020, 59, 20049, which has been published in final form at https://doi.org/10.1002/anie.202007371. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Pyridine‐substituted alkylidenecyclopropanes (Py‐ACPs) react with gold(III) salts under mild reaction conditions through an unprecedented, proximal ring‐opening pathway, to generate highly appealing, catalytically active pyridine alkenyl [C^N]‐gold(III) species. Mechanistic studies reveal that the activation of the C−C bond of the ACP takes place through an unusual concerted, σ‐bond metathesis type‐processWe thank the European Research Council (ERC Starting grant agreement no. 307948, and Advanced Grant 340055), the Swiss National Science Foundation (SNF 200020_146853), the Legerlotz Stiftung the MINECO (SAF2016‐76689‐R, CTQ2017‐84767‐P), the Xunta de Galicia (2015‐CP082, ED431C 2017/19, and Centro singular de investigación de Galicia accreditation 2019–2022, ED431G 2019/03) and the European Union (European Regional Development Fund—ERDF) for financial support and the STSM Grant to F. Verdugo from COST Action CA15106S