Base-Induced Sulfoxide-Sulfenate Rearrangement of 2-Sulfinyl Dienes for the Regio- and Stereoselective Synthesis of Enantioenriched Dienyl Diols

The base-induced [2,3]-sigmatropic rearrangement of a series of enantiopure 2-sulfinyl dienes has been examined and optimized using a combination of NaH and iPrOH. The reaction takes place by allylic deprotonation of the 2-sulfinyl diene to give a bis-allylic sulfoxide anion intermediate that after protonation undergoes sulfoxide-sulfenate rearrangement. Different substitution at the starting 2-sulfinyl dienes has allowed us to study the rearrangement finding that a terminal allylic alcohol is determinant to achieve complete regioselectivity and high enantioselectivities (90:10-95:5) with the sulfoxide as the only element of stereocontrol. Density functional theory (DFT) calculations provide an interpretation of these resultsThe authors thank MICINN (PID2019-107380GB-I00) for financial support. M.M. thanks Erasmus+ program for an internship. The authors thank Paula López and Fernando Romero for their initial experiments with compounds 8, 9, and 11. They also thank the Centro de Computación Científica at the UAM for their generous allocation of computer tim

Pd-catalyzed δ-C(sp3)−H thiolation of amino acid derivatives

Herein, we report a protocol for the selective δ-thiolation of aliphatic α-amino acids catalyzed by a Pd(II)/Ag(I) system. This reaction employs disulfides as thiolating agents and N-COPy as directing group, providing valuable non-proteinogenic amino acid derivatives in moderate to good diastereoselectivities and yields. Remarkably, the method is also suitable for the late-stage functionalization of a dipeptide. Experimental and DFT studies have provided significant insights into the mechanism and underlying factors controlling the selectivity of the process and determining the key role of the silver saltPGC2018-098660-B-I00, PID2021-124853NB-10

Palladium-Catalyzed PIDA-Mediated δ-C(sp3 ) H Acetoxylation of amino acid derivatives: overriding competitive intramolecular amination

The selective δ-C(sp3)−H acetoxylation of N-(SO2Py)-protected amino acid derivatives has been accomplished by using palladium-catalysis and PhI(OAc)2 (PIDA) as both terminal oxidant and acetoxy source. The distinct structural and electronic features of the SO2Py compared to more traditional carbonyl-based directing groups is essential to override the otherwise more favourable competitive intramolecular C−H amination. The δ-site selectivity predominates over traditionally more favorable 5-membered cyclopalladation at competitive γ-CH2. Experimental and DFT mechanistic studies provide important insights about the mechanism and the underlying factors controlling the chemo- and regioselectivityWe thank the Ministerio de Ciencia e Innovación (MICINN) and Fondo Europeo de Desarrollo Regional (FEDER, UE) for financial support (Agencia Estatal de Investigación/Project PGC2018-098660-B-I00). M.M.-M. thanks MINECO for a FPI predoctoral fellowship and D.S.P. thanks Fonds der chemischen Industrie FCI (PhD fellowship) for financial suppor

Enantiospecific Synthesis of 1,3-Disubstituted Allenes from Propargylic Carbonates through a Borylation-1,2-Elimination Process

An array of enantioenriched vinyl boronates bearing an allylic carbonate moiety have been prepared through selective hydroboration of propargyl carbonates. Treatment of these vinyl boronates with TBAF in THF affords enantioenriched 1,3- disubstituted allenes through a novel 1,2-anti elimination in good yields and high enantiospecificitiesWe thank MINECO (CTQ2016-78779-R) and MICINN (PID2019-107380GB I00) for financial suppor

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Reacción de Diels-Alder asimétrica de "alfa"-Sulfinilmaleatos y "alfa"-Sulfinilcicloalquenonas enantioméricamente puros

Tesis doctoral inédita leída. Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química, 01-01 199

ExtremArte

El trabajo obtuvo un Premio Tomás García Verdejo a las buenas prácticas educativas en la Comunidad Autónoma de Extremadura para el curso 2017/2018. Modalidad BSe presenta un proyecto en el que partiendo de la mejora estética de un aula de usos múltiples se desarrollaron actividades centradas en el arte, en las que participaron alumnos de infantil, primaria, secundaria y las familias y el personal no docente del centro. Otros objetivos del proyecto fueron: desarrollar las competencias clave del alumnado y aumentar su motivación e incrementar los conocimientos y el interés por la Comunidad Autónoma de Extremadura en todos los níveles (artístico, ambiental, geográfico, deportivo, literario, histórico, etc.)ExtremaduraES