Olefinación C-H catalizada por paladio de compuestos aromáticos asistida por grupos de azufre coordinantes

Tesis doctoral inédita. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química Orgánica. Fecha de lectura: 10-05-201

Palladium-Catalyzed Remote ortho-C-H Alkenylation of Alkyl Aryl Sulfones: Access to Densely Functionalized Indane Derivatives

This is the peer-reviewed version of the following article: Advanced Synthesis and Catalysis 358.7 (2016): 1065-1072, which has been published in final form at http://dx.doi.org/10.1002/adsc.201501129. This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-ArchivingA practical method for the palladium-cat-alyzed ortho-olefination of benzyl and phenethyl 2-pyridyl sulfones with electron-deficient alkenes using N-fluoro-2,4,6-trimethylpyridinium triflate ([F+]) as the terminal oxidant is described. The che-lating auxiliary (2-pyridyl)sulfonyl unit was demon-strated to be the key to the success of this reaction, which occurs efficiently with excellent regioselectiv-ity and monosubstitution selectivity. A variety of steric and electronic changes to both coupling part-ners is tolerated, including substitution at the ben-zylic position of the sulfone compound. Further-more, no appreciable loss of enantiopurity is ob-served when using non-racemic substrates. This method provides access to indane derivatives hold-ing three contiguous stereogenic centers with high diastereocontrol. The indane framework was con-structed by intramolecular Michael addition of the a-sulfonyl carbanion to the electrophilic alkeneWe thank the Spanish Government (MINECO, CTQ2012- 35790) for financial support. P.D. L. thanks the Spanish Government (MINECO) for an FPU predoctoral fellowshi

Potential of (2E,7E)-Nonadienedioates in Asymmetric Synthesis: Construction of Homopipecolic Acid and an Aminoester Building Block for Peptide Nucleic Acids

[ES]Se describe la adición asimétrica de Michael de (R)-N-bencil-N-alfa- metilbencilamiduro de litio al diester ortogonalmente sustituido (2E,7E)-nonadienedioato de hidrogeno y metilo para obtener un aducto de monoadición que por posterior manipulación del doble enlace remanente conduce a una síntesis eficaz de ácido (R)-homopipecolico y monomeros utiles en la sintesis de ácidos péptido nucleicos.MICINN (EUI2008-00173), MEC (CTQ2009-11172/BQU), FSE and Junta de Castilla y León (Spain): (SA001A09) y Grupo de Excelencia GR-17

Using Plant-Based Preparations to Protect Common Bean against Halo Blight Disease: The Potential of Nettle to Trigger the Immune System

[EN] Halo blight disease of beans (Phaseolus vulgaris L.), caused by the bacterium Pseudomonas syringae pv. phaseolicola (Pph), is responsible for severe losses in crop production worldwide. As the current agronomic techniques used are not effective, it is necessary to search for new ones which may prevent disease in common bean. In this study, we challenged four plant-based preparations (PBPs), with no other agronomic uses, as they come from industrial waste (grapevine pomace (RG) and hop residue (RH)) or wild plants (Urtica dioica (U) and Equisetum sp. (E)), to be used as immune defense elicitors against Pph in common bean. After studying their inhibitory effect against Pph growth by bioassays, the two most effective PBPs (RG and U) were applied in common bean plants. By measuring the total H2O2, lipid peroxidation, and antioxidant enzymatic activities, as well as the expression of six defense-related genes—PR1, WRKY33, MAPKK, RIN4, and PAL1—, it was observed that U-PBP application involved a signaling redox process and the overexpression of all genes, mostly PR1. First infection trials in vitro suggested that the application of U-PBP involved protection against Pph. The elicitation of bean defense with U-PBP involved a decrease in some yield parameters, but without affecting the final production. All these findings suggest a future use of U-PBP to diminish halo blight disease.SIThis research was funded by the Spanish Ministry of Economy, Industry and Competitiveness, grant number RTC-2016-5816-2

Cu-Catalyzed Silylation of Alkynes: A Traceless 2-Pyridylsulfonyl Controller Allows Access to either Regioisomer on Demand

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of the American Chemical Society, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/jacs.5b02667The Cu-catalyzed silylation of terminal and internal alkynes bearing a 2-pyridyl sulfonyl group (SO2Py) at the propar-gylic position affords a breadth of vinyl silanes in good yields and excellent regio- and stereocontrol under mild conditions. The directing SO2Py group is essential in terms of reaction efficiency and chemoselectivity. Importantly, this group also provides the ability to reverse the regiochemical outcome of the reaction, opening the access to either regioisomer without modification of the starting substrate by virtue of an in situ base-promoted alkyne to allene equilibration which takes place prior to the silylcupration process. Furthermore, removal of the directing SO2Py allows for further elaboration of the silylation products. In particular, a one-pot tandem alkyne silylation/allylic substitution sequence, in which both steps are catalyzed by the same Cu species, opens up a new approach for the access to either formal hydrosilylation regioisomer of unsymmetrical aliphatic-substituted internal alkynes from propargyl sulfonesThis work was supported by the Ministerio de Economía y Com-petitividad (MINECO, CTQ2012-35790) and the European Union for a Marie Curie Career Integration Grant (to P.M). J. R. and P.M. thank MINECO for a FPI predoctoral fellowship and a Ramón y Cajal contract, respectivel

Immune Priming Triggers Cell Wall Remodeling and Increased Resistance to Halo Blight Disease in Common Bean

[EN] The cell wall (CW) is a dynamic structure extensively remodeled during plant growth and under stress conditions, however little is known about its roles during the immune system priming, especially in crops. In order to shed light on such a process, we used the Phaseolus vulgaris- Pseudomonas syringae (Pph) pathosystem and the immune priming capacity of 2,6-dichloroisonicotinic acid (INA). In the first instance we confirmed that INA-pretreated plants were more resistant to Pph, which was in line with the enhanced production of H2O2 of the primed plants after elicitation with the peptide flg22. Thereafter, CWs from plants subjected to the different treatments (non- or Pph-inoculated on non- or INA-pretreated plants) were isolated to study their composition and properties. As a result, the Pph inoculation modified the bean CW to some extent, mostly the pectic component, but the CW was as vulnerable to enzymatic hydrolysis as in the case of non-inoculated plants. By contrast, the INA priming triggered a pronounced CW remodeling, both on the cellulosic and non-cellulosic polysaccharides, and CW proteins, which resulted in a CW that was more resistant to enzymatic hydrolysis. In conclusion, the increased bean resistance against Pph produced by INA priming can be explained, at least partially, by a drastic CW remodeling.SIThis research was funded by the Spanish Ministry of Economy, Industry and Competitiveness, grant number RTC-2016-5816-2

Optoelectronic analysis of technical factors and performance of elite-level air pistol shooting.

Technical elements are related to shooting performance; however, the importance of each factor regarding performance, especially in elite-level pistol shooters, remains controversial. The objective of this study was to determine the technical factors that influence pistol performance. One elite-level shooter was analysed during the season before the Olympic classification European championship through a total of six competitions (n = 360 shots). Aiming point trajectories were measured with the SCATT optoelectronic system. Variables were classified into six categories: performance; aiming time; stability of hold; aiming accuracy; cleanness of triggering and shooting delta. Principal component analysis, multiple regressions, Pearson correlations and ANOVAs were used to analyse the data. The results showed that five components (aiming time, stability of hold, aiming accuracy, cleanness of triggering and shooting delta) determined a total of 79.68% of the shooting variance. Specifically, aiming accuracy and cleanness of triggering explained up to 25% of the shooting score, with cleanness of triggering serving as the determining factor. Correlations were found among the performance and stability of hold, aiming accuracy, cleanness of triggering and shooting delta. Last, significant differences were found among 8-score, 9-score and 10-score shots. We conclude that while aiming accuracy seems to be related to the performance, cleanness of triggering could be the most critical technical element; furthermore, while stability of hold does not seem to be a determining factor of the score, it could be a general prerequisite to achieve high levels of performance in elite-level air pistol shooters.post-print470 K

Influence of the use of resin on the velocity and precision of handball throws

El manejo del balón se considera determinante en la precisión y potencia de los lanzamientos en balonmano. Para facilitar este manejo, el reglamento permite utilizar un material adhesivo denominado “resina” a los jugadores. El propósito del estudio fue analizar la influencia de la resina sobre la velocidad y precisión del lanzamiento, tanto en hombres como en mujeres en etapas formativas (sub-18) y sénior. La muestra estuvo compuesta por 46 jugadores (31 hombres y 15 mujeres) que realizaron un protocolo de 6 lanzamientos a distancia con la intención de aplicar la máxima velocidad y precisión. De forma aleatoria, cada sujeto lanzó 3 veces sin resina, y otras 3 con resina. Los resultados mostraron una mayor velocidad con el uso de resina en el total de la muestra analizada. Los lanzamientos con resina fueron un 6,56% más veloces (p 0,05). Además, no se encontraron diferencias entre los subgrupos de análisis (p > 0,05). Por tanto, el uso de resina parece ser determinante en la velocidad de lanzamiento. Estos resultados son de elevada aplicación práctica tanto en el ámbito del entrenamiento deportivo como para la valoración de la importancia del lanzamiento en el rendimiento ofensivo de un equipo de balonmano.The handling of the ball is considered to be a determining factor in the precision and power of handball throws. To facilitate ball handling, the rules allow players to use an adhesive material called ‘resin’. The aim of the study was to analyse the influence of the resin on the throw velocity and accuracy, both in men and women in formative (U-18) and senior categories. The sample consisted of 46 players (31 men and 15 women) who performed a protocol of 6 distance throws with the intention of maximum velocity and accuracy. Randomly, each subject threw 3 times without resin and 3 times with resin. The results showed a higher velocity with the use of resin in the whole sample analysed. Throws with resin were 6.56% faster (p 0,05). Furthermore, no differences were found between the analysis subgroups (p > 0.05). The use of resin seems to be a determinant of throwing velocity. These results are highly applicable both in the field of sport training and for the evaluation of the importance of the throw in the offensive performance of a handball team.peerReviewe

The Relative Age Effect on Competition Performance of Spanish International Handball Players: A Longitudinal Study

Background: Competitive success is the ultimate objective of elite professional sport organisations. Relative age effects (RAE) impact athlete selection processes in the short and long-term performance. The aims of this study were: (i) examine the presence of RAE by gender, competitive level, and playing position, as well as evaluate the impact of RAE on individual (goals, percentage of effectiveness in shots, saves; percentage of effectiveness in saves, assists, turnovers, steals, blocked shots, penalties, minutes played, and minutes played per match) and collective competition performance (final team position); and (ii) analyse the impact of RAE on the evolutionary trends of individual performance in international competitions throughout 16 seasons in Spanish handball (2005–2020). Methods: The sample included 631 Spanish handball players (male: n = 359; female: n = 272). A Chi-square goodness-of-fit test was used to assess whether a skewed birthdate distribution occurred. A one-way analysis of variance (ANOVA) of independent measures was used to examine the individual and collective statistical parameters by birth quartiles. A linear regression in a Hopkins sheet were performed to compare individual performance trends. Results: The results revealed RAE in the male formative categories (p < 0.001), as well as the male and female senior categories (p < 0.05). By position, RAE especially affected the “centre-back” in the male formative (p < 0.01) and senior categories (p < 0.05). No significant relationship between RAE and individual performance was found in male formative categories, while an impact of RAE on the “minutes played” was detected in the female senior category (p < 0.05). With regard to collective performance, a higher number of relatively older handball players was observed in the best ranked teams in the male formative categories and in the quarter-final teams in the female formative categories (p < 0.05). Among the male players, relatively older players spent more minutes on the court than relatively younger players, although this advantage dissipated over time and did not lead to better performance. Among the female players, relatively younger players were found to perform better as the level of competitive handball increased. Discussion: These findings are important for talent identification and development policies in sport federations and other elite sport institutions by demonstrating the many unintended consequences of selections to international competitions at the youth level

Deciphering the enzymatic target of a new family of antischistosomal agents bearing a quinazoline scaffold using complementary computational tools.

A previous phenotypic screening campaign led to the identification of a quinazoline derivative with promising in vitro activity against Schistosoma mansoni. Follow-up studies of the antischistosomal potential of this candidate are presented here. The in vivo studies in a S. mansoni mouse model show a significant reduction of total worms and a complete disappearance of immature eggs when administered concomitantly with praziquantel in comparison with the administration of praziquantel alone. This fact is of utmost importance because eggs are responsible for the pathology and transmission of the disease. Subsequently, the chemical optimisation of the structure in order to improve the metabolic stability of the parent compound was carried out leading to derivatives with improved drug-like properties. Additionally, the putative target of this new class of antischistosomal compounds was envisaged by using computational tools and the binding mode to the target enzyme, aldose reductase, was proposed