Organocatalytic strategies for the development of the enantioselective inverse-electron-demand hetero-Diels-Alder reaction

Cycloaddition reactions, in particular Diels-Alder reactions, have attracted a lot of attention from organic chemists since they represent one of the most powerful methodologies for the construction of carbon-carbon bonds. In particular, inverse-electron-demand hetero-Diels-Alder reactions have been an important breakthrough for the synthesis of heterocyclic compounds. Among all their variants, the organocatalytic enantioselective version has been widely explored since the asymmetric construction of diversely functionalized scaffolds under reaction conditions encompassed within the green chemistry field is of great interest. In this review, a profound revision on the latest advances on the organocatalytic asymmetric inverse-electron demand hetero-Diels-Alder reaction is shownWe are grateful to the Spanish Government (CTQ2015-64561-R and RTI2018-095038-B-I00), “Comunidad de Madrid” and European Structural Funds (S2018/NMT-4367). J.A.F.-S. thanks the Spanish Government for a Ramón y Cajal contract. V.L.-M. thanks Universidad Autónoma de Madrid for a predoctoral fellowship (FPI-UAM

Maximum rainfall intensity analysis using L-moments in Spain

Proceedings of the Seventh International Conference on Hydroscience and Engineering, Philadelphia, PA, September 2006. http://hdl.handle.net/1860/732Flood predictions are frequently the basis for engineering works, structures design, and land use planning, but quite often there are no gauged stations and consequently hydrometeorological models become an essential tool. These models require maximum rainfall intensity estimations -for different durations and return periods -an IDF law-. The IDF law actually used in Spain was developed in the seventies and it was based on an at-site analysis on the 21 available gauged stations in that moment, using Gumbel distribution for adjustment. Last paragraph is an invitation to revising methodology and updating data as nowadays there are more gauged stations with sufficient records in the Spanish peninsular area. However, classical approach to the regionalization technique cannot be used due to scarce stations -there are 63 stations in 500.000 km2- and great climate variability in short distances -from semi-arid in the southeast to Atlantic climate in the north-. Thus, authors propose an “intra-station” regionalization, it is to say, a regionalization in the same station. Besides, they suggest new expressions in order to extend results to the rest of the territory. According to practical character of this study, a GIS (geographical information system) application was developed –MAXIN- and it is available in: http://www.forestales.upm.es/hidraulica/paginas/programas/programas.ht

Power quality events detection using fourth-order spectra

This paper introduces the use of a fourth-order frequency-domain statistical estimator, the spectral kurtosis (SK), in the field of power-quality analysis. The research has been organized in the frame of a research national project and points towards the implementation of these techniques into an automatic platform to perform PQ analysis in power plants and power inverters. Higher-order statistics in the frequency domain manage to distinguish 3 types of electrical anomalies (sags, swells and transients), with an accuracy of 83%

Exogenous Measurements from Basic Meteorological Stations forWind Speed Forecasting

This research presents a comparative analysis of wind speed forecasting methods applied to perform 1 h-ahead forecasting. The main significant development has been the introduction of low-quality measurements as exogenous information to improve these predictions. Eight prediction models have been assessed; three of these models [persistence, autoregressive integrated moving average (ARIMA) and multiple linear regression] are used as references, and the remaining five, based on neural networks, are evaluated on the basis of two procedures. Firstly, four quality indices are assessed (the Pearson’s correlation coefficient, the index of agreement, the mean absolute error and the mean squared error). Secondly, an analysis of variance test and multiple comparison procedure are conducted. The findings indicate that a backpropagation network with five neurons in the hidden layer is the best model obtained with respect to the reference models. The pair of improvements (mean absolute-mean squared error) obtained are 29.10%–56.54%, 28.15%–53.99% and 4.93%–14.38%, for the persistence, ARIMA and multiple linear regression models, respectively. The experimental results reported in this paper show that traditional agricultural measurements enhance the predictions

Enantioselective inverse-electron demand Aza-Diels-Alder reaction: ipso,α-selectivity of silyl dienol ethers

A highly efficient enantioselective inverse-electron-demand aza-Diels-Alder reaction between aza-sulfonyl-1-aza-1,3-butadienes and silyl (di)enol ethers has been developed. The presented methodology allows the synthesis of benzofuran-fused 2-piperidinol derivatives with three contiguous stereocenters in a highly selective manner, as even the hemiaminal center is completely stereocontrolled. Density functional theory (DFT) calculations support that the hydrogen-bond donor-based bifunctional organocatalyst selectively triggers the reaction through the ipso,α-position of the dienophile, in contrast to the reactivity observed for dienolates in situ generated from β,γ-unsaturated derivatives. Moreover, the calculations have clarified the mechanism of the reaction and the ability of the hydrogen-bond donor core to hydrolyze selectively theEisomer of the dienol ether. Furthermore, to demonstrate the applicability of silyl enol ethers as nucleophiles in the asymmetric synthesis of interesting benzofuran-fused derivatives, the catalytic system has also been implemented for the highly efficient installation of an aromatic ring in the piperidine adductsFinancial support was provided by the European Research Council (ERC-CoG, contract number: 647550), Spanish Government (RTI2018-095038-B-I00), and “Comunidad de Madrid” and European Structural Funds (S2018/NMT-4367

Asymmetric synthesis of Rauhut-Currier-type esters via Mukaiyama-Michael reaction to acylphosphonates under bifunctional catalysis

A highly enantioselective organocatalytic Mukaiyama-Michael reaction of silyloxy dienes and α,β-unsaturated acyl phosphonates under bifunctional organocatalysis is presented. The new reactivity triggered by the catalyst conducted to Rauhut-Currier type esters, via a formal conjugate addition to α,β-unsaturated esters. This protocol proceeds under mild conditions with complete regioselectivity and excellent enantiocontrolWe are grateful to the Spanish Government (CTQ2015-64561-R and CTQ2016-76061-P) and the European Research Council (ERCCG-UNBICAT, contract number: 647550). J. A. F.-S. and V. L.-M. thank the Spanish Government for a Juan de la Cierva Contract and the Universidad Auto´noma de Madrid for a predoctoral fellowship (FPI-UAM), respectively. Financial support from the Spanish Ministry of Economy and Competitiveness, through the ‘‘Maria de Maeztu’’ Program of Excellence in R&D (MDM-2014-0377), is also acknowledged. We acknowledge the generous allocation of computing time at the CCC (UAM

Isothiourea-catalysed enantioselective radical conjugate addition under batch and flow conditions

Financial support was provided by the Spanish Government (RTI2018-095038-B-I00), “Comunidad de Madrid” for European Structural Funds (S2018/NMT-4367) and proyectos sinergicos I+D (Y2020/NMT-6469). J. A. F.-S. thanks the Spanish Government for a Ramón y Cajal contract. The research leading to these results has received funding from the EaSI-CAT centre for Doctoral Training (M.T.W) and Carlsberg Foundation (M.J.).The photocatalytic generation of α-amino radicals is combined with chiral isothiourea derived α,β-unsaturated acyl ammonium intermediates. The reaction proceeds via a [3+2] radical-polar crossover mechanism to generate γ-lactams in good yields and enantioselectivities. The enantioselective radical conjugate addition was carried out under batch and flow conditions.Publisher PDFPeer reviewe

Strong-LAMP Assay Based on a Strongyloides spp.-Derived Partial Sequence in the 18S rRNA as Potential Biomarker for Strongyloidiasis Diagnosis in Human Urine Samples

Human strongyloidiasis a soil-transmitted infection caused by Strongyloides stercoralis is one of the most neglected amongst the so-called Neglected Tropical Diseases (NTDs). S. stercoralis is a nematode, which is distributed worldwide; it has been estimated that it could affect millions of people, mainly in tropical and subtropical endemic regions. The difficulties of diagnosis lead to infection rates being underreported. Asymptomatic patients have chronic infections that can lead to severe hyperinfection syndrome or disseminated strongyloidiasis in immunocompromised patients. Strongyloidiasis can easily be misdiagnosed because conventional faecal-based techniques lack of sensitivity for the morphological identification of infective larvae in faeces. None of the currently used molecular methods have used urine samples as an alternative to faecal samples for diagnosing strongyloidiasis. This study was thus aimed at comparing, for the first time, the use of a new loop-mediated isothermal amplification (LAMP) molecular assay (Strong-LAMP) to traditional methods on patients' urine samples. Twenty-four urine samples were taken from patients included in a study involving two Spanish hospitals for strongyloidiasis screening using parasitological and serological tests. Strongyloides larvae were found in 11 patients' faecal samples, thereby ascertaining that they had the disease. Other patients had high antibody titres but no larvae were found in their faeces. All urine samples were analysed by PCR and Strong-LAMP assay. No amplification occurred when using PCR. Strong-LAMP led to detecting S. stercoralis DNA in urine samples from patients having previously confirmed strongyloidiasis by parasitological tests and/or a suspicion of being infected by serological ones. The Strong-LAMP assay is a useful molecular tool for research regarding strongyloidiasis in human urine samples. After further validation, the Strong-LAMP assay could also be used for complementary and effective diagnosis of strongyloidiasis in a clinical setting

Characterization and engineering of the biosynthesis gene cluster for antitumor macrolides PM100117 and PM100118 from a marine actinobacteria: generation of a novel improved derivative

Additional file 1: Figure S1. Sequence alignment of the cluster PKS domains active sites. LD, loading domain; M1-M20, extension modules. Polyketide synthase domains are as follows: KS, ketosynthase; AT, acyltransferase; KR, ketoreductase; DH, dehydratase; ER, enoilreductase; ACP, acyl carrier protein; CAL, CoA-ligase. Figure S2. Genetic complementation of mutant strains. UPLC analysis of PM100117 (1) and PM100118 (2) production in strains GUA-pS, CPgonP8, CPgonM4, CPgonMT, CPgonSL, CPgonS1, CPgonS2, CPgonCP, CPgonMR and CPgonL1. Figure S3. Antibiotic activity test of compound 5. Diffusion disc assay against Saccharomyces cerevisiae and Micrococcus luteus. The length (cm) of the inhibition-growth halo is indicated by numbers and yellow lines. Methods S2. Antibiotic activity assay. Format: PDF

Factors associated with successful dietary changes in an energy-reduced Mediterranean diet intervention: a longitudinal analysis in the PREDIMED-Plus trial

Purpose Long-term nutrition trials may fail to respond to their original hypotheses if participants do not comply with the intended dietary intervention. We aimed to identify baseline factors associated with successful dietary changes towards an energy-reduced Mediterranean diet (MedDiet) in the PREDIMED-Plus randomized trial. Methods Longitudinal analysis of 2985 participants (Spanish overweight/obese older adults with metabolic syndrome) randomized to the active intervention arm of the PREDIMED-Plus trial. Dietary changes were assessed with a 17-item energy-reduced MedDiet questionnaire after 6 and 12 months of follow-up. Successful compliance was defined as dietary changes from baseline of ≥ 5 points for participants with baseline scores < 13 points or any increase if baseline score was ≥ 13 points. We conducted crude and adjusted multivariable logistic regression models to identify baseline factors related to compliance. Results Consistent factors independently associated with successful dietary change at both 6 and 12 months were high baseline perceived self-efficacy in modifying diet (OR6-month: 1.51, 95% CI 1.25–1.83; OR12-month: 1.66, 95% CI 1.37–2.01), higher baseline fiber intake (OR6-month: 1.62, 95% CI 1.07–2.46; OR12-month: 1.62, 95% CI 1.07–2.45), having > 3 chronic conditions (OR6-month: 0.65, 95% CI 0.53–0.79; OR12-month: 0.76, 95% CI 0.62–0.93), and suffering depression (OR6-month: 0.80, 95% CI 0.64–0.99; OR12-month: 0.71, 95% CI 0.57–0.88). Conclusion Our results suggested that recruitment of individuals with high perceived self-efficacy to dietary change, and those who initially follow diets relatively richer in fiber may lead to greater changes in nutritional recommendations. Participants with multiple chronic conditions, specifically depression, should receive specific tailored interventions