Synthesis of α-functionalized α-indol-3-yl carbonyls through direct SN reactions of indol-3-yl α-acyloins

A new and efficient synthesis of α-functionalized α-indol-3-yl ketones from easily available indolyl α-acyloins is reported. This process, catalyzed by Brønsted or Lewis acids, involves an uncommon direct nucleophilic substitution reaction of a secondary α-carbonyl-substituted hydroxyl group. The described methodology allows the introduction of a variety of nucleophiles such as (hetero)arenes, thiophenols, nitroanilines and 1,3-dicarbonyl derivatives. The synthesized α-indol-3-yl carbonyl compounds are important synthetic targets also useful for accessing functionalized tryptophols and furan-3-yl indoles.Ministerio de Economía y Competitividad (MINECO) (CTQ2013-48937-C2-1-P) and Junta de Castilla y León and FEDER (BU237U13 and BU076U16

Uso de un compuesto de fórmula (I) como bactericida frente a Streptococcus

Uso de al menos un compuesto de fórmula (I) donde R1 es alquilo C1-C6 o forma Ncicloalquilo C5-C8 junto con R2 ; R 2 es alquilo C1-C6, forma Ncicloalquilo C5-C8 junto con R1 , o es una cadena alquílica que se une a (CH2)n formando una amina bicíclica; R3 es alquilo C1-C2 o ausente; R4 es un sustituyente aromático que comprende al menos dos anillos aromáticos; n es un valor entre 1 y 2; y m es un valor entre 0 y 1; como bactericida frente a Streptococcus, preferiblemente frente a Streptococcus pneumoniae. Adicionalmente, compuesto de fórmula (Ia) y una composición bactericida que lo comprenda.Peer reviewedConsejo Superior de Investigaciones Científicas, Universidad Miguel HernándezB1 Patente sin examen previ

Auranofin-loaded nanoparticles as a new therapeutic tool to fight streptococcal infections

Drug-loaded nanoparticles (NPs) can improve infection treatment by ensuring drug concentration at the right place within the therapeutic window. Poly(lactic-co-glycolic acid) (PLGA) NPs are able to enhance drug localization in target site and to sustainably release the entrapped molecule, reducing the secondary effects caused by systemic antibiotic administration. We have loaded auranofin, a gold compound traditionally used for treatment of rheumatoid arthritis,into PLGA NPs and their efficiency as antibacterial agent against two Gram-positive pathogens, Streptococcus pneumoniae and Streptococcus pyogenes was evaluated. Auranofin-PLGA NPs showed a strong bactericidal effect as cultures of multiresistant pneumococcal strains were practically sterilized after 6 h of treatment with such auranofin-NPs at 0.25 μM. Moreover, this potent bactericidal effect was also observed in S. pneumoniae and S. pyogenes biofilms, where the same concentration of auranofin-NPs was capable of decreasing the bacterial population about 4 logs more than free auranofin. These results were validated using zebrafish embryo model demonstrating that treatment with auranofin loaded into NPs achieved a noticeable survival against pneumococcal infections. All these approaches displayed a clear superiority of loaded auranofin PLGA nanocarriers compared to free administration of the drug, which supports their potential application for the treatment of streptococcal infections

Factors influencing board of directors’ decision-making process as determinants of CSR engagement

[EN] This paper focuses on the determinants of Corporate Social Responsibility (CSR) at the organisational level. Specifically, it aims to understand the influence of not previously analysed board of directors’ characteristics on a company’s CSR engagement. A random effect probit model was applied to a panel of Spanish non-financial and non-insurance listed firms over the period 2009–2013. The analyses revealed that the existence of a board sub-committee responsible for social and environmental matters and its size, the establishment of a statutory term limit for independent directors and the possibility for directors of receiving advice from external sources positively affect a firm’s CSR engagement. This paper contributes to the debate about corporate governance and CSR by relating factors determining the decision-making process at boards of directors to CSR. Thus, it extends research on the board as a driver for social and environmental issues and suggests new ways to deal with this issue empirically.SIThe authors acknowledge the funding received from the Project ECO2015-63880-Rfrom the Ministerio de Economı ́a y Competitividad of Spain and the Project ULE2014-1 from theUniversity of Leo ́n (Spain). They also acknowledge funding from Project ECO 2015-69058-R

The Importance of Firm Size and Development Strategies for CSR Formalisation

[EN] Despite the relevance of firm size in the analysis of corporate social responsibility (CSR) engagement, there is still much to know about the specific impact of firm size on CSR formalisation. Moreover, in order to better understand such a relation, the interaction effects of development strategies on which companies may base its growth, namely diversification and internationalisation, will be also taken into account. Specifically, this work contributes to shed light on these issues by combining theories related to external and internal drivers of CSR. Using a sample of Spanish listed firms, the results show that firm size affects positively CSR formalisation, and that this effect is stronger in the case of adopting a diversification strategy, while no evidence was found for the moderating effect of internationalisation strategy

Straight access to highly fluorescent angular indolocarbazoles via merging Au- and Mo-catalysis

A straightforward and efficient synthesis of the two less explored types of indolocarbazoles has been developed. Two different processes for the carbazole nucleus preparation, a gold-catalysed regioselective cyclization followed by the dioxomolybdenum-catalysed version of Cadogan reductive cyclization, enables the sequential construction of two carbazole cores. The procedure features total regioselectivity and high overall yields. The required starting α-indol-3-ylalkyl propargylic alcohols are easily and efficiently accessed from commercially available reagents. In addition, the photoluminescent properties of two indolo[2,3-c]carbazoles, with fluorescence quantum yields around 0.7, have been studied.Junta de Castilla y León and FEDER (BU291P18) and Ministerio de Ciencia e Innovación and FEDER (CTQ2016-75023-C2-1-P

“Back‐to‐Front” Indole and Carbazole Synthesis from N,N‐Bis‐(2‐bromoallyl)amines by Combining Carbolithiation Reactions with Gold‐Catalysis

The combination of organolithium chemistry with gold catalysis has enabled the development of a synthetic strategy for accessing polysubstituted indoles and carbazoles from readily available starting materials. This method is based on a “back-to-front” approach from ketopyrroles, generated by intramolecular carbolithiation of N,N-bis-(2-lithioallyl)amines that evolve into 3,4-bis(lithiomethyl)dihydropyrrole intermediates capable of reacting with carboxylic esters and Weinreb amides. These ketopyrroles have demonstrated to be excellent precursors of mono or bis(alkynols)pyrroles that, under gold-catalysis, experience a benzannulation reaction providing access to regioselectively substituted indoles or carbazoles.We gratefully acknowledge Ministerio de Ciencia e Innovación MCIN/AEI/10.13039/501100011033 (PID2020-115789GBC21), and Junta de Castilla y León and FEDER (BU049P20) for financial support. The project leading to these results has received funding from “la Caixa” Foundation, under the Agreement LCF/PR/PR18/51130007> (CAIXA-UBU001). M.A.M., F.M.-L., M.S. and S.S.-P. thank Junta de Castilla y León (Consejería de Educación) and Fondo Social Europeo for predoctoral (M.A.M, F.M.-L. and M.S.) and postdoctoral (S.S.- P.) contracts, respectively

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

The cyclization of o-(alkynyl)-3-(methylbut-2-enyl)benzenes, 1,6-enynes having a condensed aromatic ring at C3–C4 positions, has been studied under the catalysis of cationic gold(I) complexes. The selective 6-endo-dig mode of cyclization observed for the 7-substituted substrates in the presence of water or methanol giving rise to hydroxy(methoxy)-functionalized dihydronaphthalene derivatives is highly remarkable in the context of the observed reaction pathways for the cycloisomerizations of 1,6-enynes bearing a trisubstituted olefinMinisterio de Ciencia e Innovación (MICINN) and FEDER (CTQ2010-15358

NIS/HFIP‐Mediated Synthesis of Indene‐Based β‐Iodoalkenyl Sulfides from Propargylic Sulfides

A tandem 1,3-sulfur migration followed by iodocyclization reaction of propargylic sulfides in the presence of NIS in HFIP has been developed to synthesize indene-based β-iodoalkenyl sulfides. The choice of the reaction media is crucial to promote the reaction. The proposed mechanism involving the initial NIS activation by HFIP and favoring the sulfur migration of the starting propargylic thioether via cationic intermediates is experimentally supported. In addition, the suitability of selected indene-based β-iodoalkenyl sulfides as building blocks for subsequent C C bond-forming reactions has been demonstrated.We gratefully acknowledge MICINN (PID2020-115789GBC21); and “NextGenerationEU/PRTR” (PDC2021-120825- C21), and Junta de Castilla y León and FEDER (BU049P20) for financial support. The project leading to these results has also received funding from “la Caixa” Foundation, under the Agreement LCF/PR/PR18/51130007> (CAIXA-UBU001). N.V. and S.S.-P. thank Junta de Castilla y León (Consejería de Educación) and Fondo Social Europeo for predoctoral (N.V) and postdoctoral (S.S.-P.) contracts, respectively

Enzibióticos bactericidas mejorados frente a neumococo y otras bacterias

La presente invención se encuadra dentro del campo de la biotecnología. En la presente invención se presenta una secuencia polipeptídica derivada del módulo de unión a pared del enzima lítica del fago Cp7 (Cpl-7), que permite la construcción de nuevas enzimas líticas con actividad bactericida mejorada y amplio espectro. Igualmente, en esta invención se incluyen enzimas quiméricas que contienen dicho módulo de unión a pared mejorado y se dan ejemplos de su actividad frente a especies Gram-positivas y Gram-negativas.Peer reviewedConsejo Superior de Investigaciones Científicas, CIBER Enfermedades Respiratorias (CIBERES)A2 Solicitud de patente sin informe sobre el estado de la técnic