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Nové M, Kincses A, Szalontai B, Rácz B, Blair J.M.A, González-Prádena A, Benito-Lama M, Domínguez-Álvarez E, Spengler G
Microorganisms, vol. 8, nº 4 (2020)
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Infections caused by Salmonella species and Staphylococcus aureus represent major health and food industry problems. Bacteria have developed many strategies to resist the antibacterial activity of antibiotics, leading to multidrug resistance (MDR). The over-expression of drug efflux pumps and the formation of biofilms based on quorum sensing (QS) can contribute the emergence of MDR. For this reason, the development of novel effective compounds to overcome resistance is urgently needed. This study focused on the antibacterial activity of nine symmetrical selenoesters (Se-esters) containing additional functional groups including oxygen esters, ketones, and nitriles against Gram-positive and Gram-negative bacteria. Firstly, the minimum inhibitory concentrations of the compounds were determined. Secondly, the interaction of compounds with reference antibiotics was examined. The efflux pump (EP) inhibitory properties of the compounds were assessed using real-time fluorimetry. Finally, the anti-biofilm and quorum sensing inhibiting effects of selenocompounds were determined. The methylketone and methyloxycarbonyl selenoesters were the more effective antibacterials compared to cyano selenoesters. The methyloxycarbonyl selenoesters (Se-E2 and Se-E3) showed significant biofilm and efflux pump inhibition, and a methyloxycarbonyl selenoester (Se-E1) exerted strong QS inhibiting effect. Based on results selenoesters could be promising compounds to overcome bacterial MDR. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Uriel C, Permingeat C, Ventura J., Avellanal-Zaballa E, Bañuelos J, García-Moreno I, Gómez A.M, López J.C.
Chemistry - A European Journal, vol. 26, nº 24, pags. 5388 - 5399 (2020)
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A series of fluorescent boron-dipyrromethene (BODIPY, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) dyes have been designed to participate, as aglycons, in synthetic oligosaccharide protocols. As such, they served a dual purpose: first, by being incorporated at the beginning of the process (at the reducing-end of the growing saccharide moiety), they can function as fluorescent glycosyl tags, facilitating the detection and purification of the desired glycosidic intermediates, and secondly, the presence of these chromophores on the ensuing compounds grants access to fluorescently labeled saccharides. In this context, a sought-after feature of the fluorescent dyes has been their chemical robustness. Accordingly, some BODIPY derivatives described in this work can withstand the reaction conditions commonly employed in the chemical synthesis of saccharides; namely, glycosylation and protecting-group manipulations. Regarding their photophysical properties, the BODIPY-labeled saccharides obtained in this work display remarkable fluorescence efficiency in water, reaching quantum yield values up to 82 \%, as well as notable lasing efficiencies and photostabilities. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Romero A, Marco-Contelles J., Ramos E.
Neural Regeneration Research, vol. 15, nº 1, pags. 30 - 35 (2020)
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There is no effective treatment to face Alzheimer's disease complexity. Multitarget molecules are a good approach against the multiple physiopathological events associated with its development and progression. In this context, N-((5-(3-(1-benzylpiperidin-4-yl) propoxy)-1- methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine (ASS234) has been tested achieving promising results. ASS234 has demonstrated to cross the blood-brain barrier in vivo, and a good in silico safety profile being less toxic than donepezil. Besides, ASS234 reversibly inhibits human acetyl- and butyryl-cholinesterase, and irreversibly inhibits human monoamine oxidase A and B. Moreover, this multitarget molecule has antioxidant and neuroprotective properties, and inhibits Αβ1-42 and Αβ1-40 self-aggregation. Inquiring about the mechanism of action, several signaling pathways related to Alzheimer's disease had been explored showing that ASS234 induces the wingless-type MMTV integration site (Wnt) family and several members of the heat shock proteins family and moreover counteracts neuroinflammatory and oxidative stress-related genes promoting the induction of several key antioxidant genes. Finally, in vivo experiments with ASS234 in C57BL/6J mice displayed its ability to reduce amyloid plaque burden and gliosis in the cortex and hippocampus, ameliorating scopolamine-induced learning deficits. Here we gather the information regarding ASS234 evaluated so far, showing its ability to face different targets, necessary to counteract a neurodegenerative disease as complex as the Alzheimer's disease. © 2020 Wolters Kluwer Medknow Publications. All rights reserved.
Sanz M.L, Ramos L.
Food Chemistry, Function and Analysis, vol. 2020-January, nº 17, pags. 38 - 80 (2020)
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This chapter reviews sample preparation techniques in use for the analysis of relevant semi-volatile and non-volatile components in liquid and solid foodstuffs. Comparison among techniques evolves from the most conventional and widely accepted ones, to recently introduced approaches which are receiving an increasing attention or are already fully incorporated to this active research field. © The Royal Society of Chemistry 2020.
Megías-Pérez R, Hahn C, Ruiz-Matute A.I, Behrends B, Albach D.C, Kuhnert N.
Food Research International, vol. 127 (2020)
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Kale (Brassica oleracea) is a cool-season vegetable widely employed in the elaboration of diverse products such as tea and smoothies in USA or in the Northern German cuisine in wintertime. Besides, kale is gaining attention due to the diverse health benefits reported in the literature for its consumption, e.g. antigenotoxic and anticarcinogenic effect, protection of cardiovascular system and gastrointestinal tract. Low molecular weight carbohydrates (LMWC) are compounds directly related with kale flavour and nutritional quality. Despite different studies focusing on the chemical composition of kale, few information on LMWC is available. Thus, in this work a multianalytical approach was conducted in order to perform a comprehensive study of kale LMWC; their evolution during plant development and acclimation to cool temperatures was also evaluated. Gas chromatography coupled to mass spectrometry allowed the identification of 13 LMWC, being myo-inositol, galactinol, maltose and melibiose described for the first time in kale. Eight major LMWC were quantified in three different commercial kale cultivars using hydrophilic interaction liquid chromatography coupled to mass spectrometry to monitor possible differences in their content during plant development and as consequence of plant acclimation to cold temperatures. Overall, for all types of kales under study, the content of maltose and sucrose decreased during the plant development while the concentration of fructose, melibiose, maltose, raffinose and galactinol was increased in all kale types exposed to low temperatures. These results underline the importance of controlling the temperature during kale cultivation in order to obtain products with a high nutritional value. © 2019 Elsevier Ltd
Escobar-Arnanz J, Sanz M.L, Ros M, Sanz J., Ramos L.
Journal of Chromatography A, vol. 1616 (2020)
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The aim of this study was to develop a statistical model based on a set of intuitive topological descriptors that will help to determine the influence of the polychlorinated biphenyls (PCBs) structural features on the chromatographic behavior of these analytes in a variety of gas chromatographic stationary phases, including the highly polar ionic liquid (IL)-based SLB-IL76 and SLB-IL60 columns. The model was developed using the stepwise multiple linear regression method, and constructed through several levels of increasing complexity to make evident the relative influence of the selected descriptors. The proposed model was easy to implement and provided similar satisfactory results irrespective of the dependent variables used (i.e., retention index or retention time) or the chromatographic conditions applied (i.e., pseudo-isotherm and programmed temperature) for IL-based phases. The model also allowed the correct prediction of the elution order of selected PCBs in these and other less polar phases evaluated (i.e., SW-10, DB-17, ZB-5 and HT-8). To our knowledge, this is the first models based on topological descriptors described in the literature that provided a satisfactory fitting of the PCB behavior in IL-based phases. Our results indicated that the mechanism governing the chromatographic separation of PCBs in these highly polar columns showed significant differences compared with those observed in other less polar stationary phases. © 2020
Herrera F, Luna A., Fernández I, Almendros P
Chemical Communications, vol. 56, nº 8, pags. 1290 - 1293 (2020)
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The controlled synthesis of 1,4-naphthoquinones and tetraphene-7,12-diones, which bear the ABCD-ring of landomycins, has been accomplished directly through oxidative rearrangement of common stable precursors, namely, previously non-isolable cyclobuta[a]naphthalen-4(2H)-ones. © The Royal Society of Chemistry.
Blázquez-Moraleja A, Sáenz-de-Santa-María I, Chiara M.-D., Álvarez-Fernández D, García-Moreno I, Prieto Montero R, Martínez Martínez V, López-Arbeloa I, Chiara J.L.
Chemical Science, vol. 11, nº 4, pags. 1052 - 1065 (2020)
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The first fluorescent probes that are actively channeled into the mitochondrial matrix by a specific mitochondrial membrane transporter in living cells have been developed. The new functional probes (BCT) have a minimalist structural design based on the highly efficient and photostable BODIPY chromophore and carnitine as a biotargeting element. Both units are orthogonally bonded through the common boron atom, thus avoiding the use of complex polyatomic connectors. In contrast to known mitochondria-specific dyes, BCTs selectively label these organelles regardless of their transmembrane potential and in an enantioselective way. The obtained experimental evidence supports carnitine-acylcarnitine translocase (CACT) as the key transporter protein for BCTs, which behave therefore as acylcarnitine biomimetics. This simple structural design can be readily extended to other structurally diverse starting F-BODIPYs to obtain BCTs with varied emission wavelengths along the visible and NIR spectral regions and with multifunctional capabilities. BCTs are the first fluorescent derivatives of carnitine to be used in cell microscopy and stand as promising research tools to explore the role of the carnitine shuttle system in cancer and metabolic diseases. Extension of this approach to other small-molecule mitochondrial transporters is envisaged. © The Royal Society of Chemistry 2020.
Martín-Mejías I, Aragoncillo C, Yanai H, Hoshikawa S, Fujimoto Y, Matsumoto T, Almendros P
Chemical Communications, vol. 56, nº 12, pags. 1795 - 1798 (2020)
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Carbazoles possessing Tf2CHCH2 groups were obtained by the reaction of 1-(indol-2-yl)but-3-yn-1-ols with in situ-generated Tf2CCH2 through vicinal difunctionalisation of the alkyne moiety, where the vinyl-type carbocation intermediate was selectively attacked by the indole moiety and not by the carbanion moiety. This journal is © The Royal Society of Chemistry.
Angona I.P, Daniel S, Martin H, Bonet A, Wnorowski A, Maj M, Jóźwiak K, Silva T.B, Refouvelet B, Borges F, Marco-Contelles J., Ismaili L.
Molecules, vol. 25, nº 6 (2020)
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We report herein the design, synthesis and biological evaluation of new antioxidant and neuroprotective multitarget directed ligands (MTDLs) able to block Ca2+ channels. New dialkyl 2,6-dimethyl-4-(4-(prop-2-yn-1-yloxy)phenyl)-1,4-dihydropyridine-3,5-dicarboxylate MTDLs 3a-t, resulting from the juxtaposition of nimodipine, a Ca2+ channel antagonist, and rasagiline, a known MAO inhibitor, have been obtained from appropriate and commercially available precursors using a Hantzsch reaction. Pertinent biological analysis has prompted us to identify the MTDL 3,5-dimethyl-2,6-dimethyl-4-[4-(prop-2-yn-1-yloxy)phenyl]-1,4-dihydro- pyridine-3,5-dicarboxylate (3a), as an attractive antioxidant (1.75 TE), Ca2+ channel antagonist (46.95\% at 10 µM), showing significant neuroprotection (38\%) against H2O2 at 10 µM, being considered thus a hit-compound for further investigation in our search for anti-Alzheimer's disease agents. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Galmés M.A, García-Junceda E, Świderek K., Moliner V.
ACS Catalysis, vol. 10, nº 3, pags. 1938 - 1946 (2020)
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Enzyme promiscuity attracts the interest of the industrial and academic sectors because of its application in the design of biocatalysts. The amidase activity of Candida antarctica lipase B (CALB) on two different substrates has been studied by theoretical quantum mechanics/molecular mechanics methods, supported by experimental kinetic measurements. The aim of the study is to understand the substrate promiscuity of CALB in this secondary reaction and the origin of its promiscuous catalytic activity. The computational results predict activation free energies in very good agreement with the kinetic data and confirm that the activity of CALB as an amidase, despite depending on the features of the amide substrate, is dictated by the electrostatic effects of the protein. The protein polarizes and activates the substrate as well as stabilizes the transition state, thus enhancing the rate constant. Our results can provide guides for future designs of biocatalysts based on electrostatic arguments. Copyright © 2019 American Chemical Society.
Colomer I, Urena M, Viso A., Fernández De La Pradilla R
Chemistry - A European Journal, vol. 26, nº 20, pags. 4620 - 4632 (2020)
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The chemo- and stereocontrolled functionalization of conjugated sulfinyl dienes in a cascade process that involves a conjugate addition, diastereoselective protonation and a [2,3]-sigmatropic rearrangement is reported. Enantioenriched 1,4-diol and 1,4-aminoalcohol derivatives are obtained in a very straightforward manner. Further functionalization of these structures, including highly stereoselective epoxidation, dihydroxylation and the stereodivergent synthesis of several polyols in a controlled fashion is described. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Cerro-Gálvez E, Roscales J.L, Jiménez B., Sala M.M, Dachs J., Vila-Costa M
Water Research, vol. 171 (2020)
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Perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) acids are ubiquitous in the oceans, including remote regions, and are toxic to fish and mammals. The impact to the lowest trophic levels of the food web, however, remains unknown. We challenged natural bacterial communities inhabiting Antarctic coastal waters (Deception Island) with PFOS and PFOA concentrations ranging from 2 ng/L to 600 ng/L that selected for tolerant taxa. After 48 h, concentrations of PFOS decreased by more than 50\% and sulfur metabolism-related transcripts were significantly enriched in the treatments suggesting desulfurization of PFOS. Conversely, no significant differences were found between initial and final PFOA concentrations. Gammaproteobacteria and Roseobacter, two abundant groups of marine bacteria, increased their relative activity after 24 h of incubation, whereas Flavobacteriia became the main contributor in the treatments after 6 days. Community activities (extracellular enzyme activity and absolute number of transcripts) were higher in the treatments than in the controls, while bacterial abundances were lower in the treatments, suggesting a selection of PFOS and PFOA tolerant community in the exposed treatments. Our results show a direct effect of PFOS and PFOA exposure on the composition and functionality of natural Antarctic marine microbial communities. While no evidence of defluorination of PFOS or PFOA was detected, probable desulfurization of PFOS depicts a direct link with the sulfur biogeochemistry of the ocean. © 2020 Elsevier Ltd
Vargas E.L, Velázquez J.A, Rodrigo E, Reinecke H, Rodriguez-Hernandez J, Fernández-Mayoralas A., Gallardo A, Cid M.B
ACS Applied Bio Materials, vol. 3, nº 4, pags. 1955 - 1967 (2020)
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Inspired by the ability of enzymes to use the surrounding hydrophobic and/or polarizable groups to modulate the pKa of a given amino acid, we designed a series of soluble polymers able to decrease the basicity of pyrrolidine (from 11.2 to 8.6 pKa units), which clearly increases its aminocatalytic activity at physiological pH in C═N bond formation reactions via ion iminium activation. Other parameters such as charge density, hydrophobic/hydrophilic balance, and aggregation state have been studied as important factors in the catalytic activity of the polymers for a given substrate. To demonstrate the utility of our approach, an optimal pyrrolidine-based catalytic polymer has been used for the formation of C-N bonds between hydrazides and free sugars as the model system for the preparation of glycoconjugates. Copyright © 2020 American Chemical Society.
Martínez-Alonso E, Escobar-Peso A, Ayuso M.I, Gonzalo-Gobernado R, Chioua M, Montoya J.J, Montaner J, Fernández I, Marco-Contelles J., Alcázar A
Antioxidants, vol. 9, nº 4, pags. 1 - 21 (2020)
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Nitrones have a well-recognized capacity as spin-traps and are considered powerful free radical scavengers, which are two important issues in hypoxia-induced oxidative stress and cell death in brain ischemia. Consequently, nitrones have been proposed as therapeutic agents in acute ischemic stroke (AIS). In this paper, we update the biological and pharmacological characterization of ISQ-201, a previously identified cholesteronitrone hybrid with antioxidant and neuroprotective activity. This study characterizes ISQ-201 as a neuroprotective agent against the hypoxia-induced ischemic injury. Transitory four-vessel occlusion and middle cerebral artery occlusion (tMCAO) were used to induce cerebral ischemia. Functional outcomes were determined using neurofunctional tests. Infarct area, neuronal death, and apoptosis induction were evaluated. In addition, ISQ-201 reactivity towards free radicals was studied in a theoretical model. ISQ-201 significantly decreased the ischemia-induced neuronal death and apoptosis, in a dose-dependent manner, showing its therapeutic effect when administered up until 6 h after post-ischemic reperfusion onset, effects that remained after 3 months from the ischemic episode. Furthermore, ISQ-201 significantly reduced infarct volume, leading to recovery of the motor function in the tMCAO model. Finally, the theoretical study confirmed the reactivity of ISQ-201 towards hydroxyl radicals. The results reported here prompted us to suggest ISQ-201 as a promising candidate for the treatment of AIS. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Mukhopadhyay M, Sampath S, Muñoz-Arnanz J, Jiménez B., Chakraborty P.
Environmental Geochemistry and Health (2020)
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Adyar and Cooum, the two rivers intersecting Chennai city, are exposed to serious pollution due to the release of large quantities of dumped waste, untreated wastewater and sewage. Sediments can act as repository for emerging organic contaminants. Hence, we have monitored the occurrence and risk associated with plasticizers [six phthalic acid esters (PAEs), bis(2-ethyl hexyl adipate) (DEHA)] and bisphenol A (BPA) in surface riverine sediments of Adyar and Cooum rivers from residential/commercial, industrial and electronic waste recycling sites. Σ7plasticizers (PAEs + DEHA) in the Adyar riverine sediment (ARS) and Cooum riverine sediment (CRS) varied between 51.82–1796 and 28.13–856 ng/g, respectively. More than three-fourth of Σ7plasticizers came from bis(2-ethylhexyl) phthalate (DEHP), in accordance with the high production and usage of this compound. BPA varied between 10.70–2026 and 7.58–1398 ng/g in ARS and CRS, respectively. Average concentrations of plasticizers and BPA were four times higher in electronic waste (e-waste) recycling sites when compared with industrial and residential/commercial sites. BPA and DEHP showed a strong and significant correlation (R2 = 0.7; p < 0.01) in the e-waste sites thereby indicating common source types. Sites present at close proximity to raw sewage pumping stations contributed to 70\% of the total BPA observed in this study. For the derived pore water concentration of plasticizers and BPA, the ecotoxicological risk has been found to be higher in ARS over CRS. However, sediment concentrations in all the sites of ARS and CRS were much below the recommended serious risk concentration for human (SRChuman) and serious risk concentration for ecotoxicological (SRCeco). © 2020, Springer Nature B.V.
Monterde C, Pintado-Sierra M, Navarro R, Sánchez F, Iglesias M
ACS Applied Materials and Interfaces, vol. 12, nº 13, pags. 15108 - 15114 (2020)
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This paper reports a simple approach for the preparation of new photo-active conjugated porous polymers (CPPs) based on phenanthrene building blocks with a high Brunauer-Emmett-Teller (BET) surface area. Starting from 2,7-diiodophenanthrene-9,10-dione and its bis-dioxolane derivative with different alkynyl comonomers, we prepared a series of CPPs by C-C Sonogashira-Hagihara coupling activated by microwaves. Moreover, we demonstrated that these functionalized CPPs after hydrolysis to the corresponding diketones show much higher BET surface areas than those obtained directly from the phenanthrene-9,10-dione monomer. Reaction of diketone-hydrolyzed polymers with 2,4-difluoro-6-hydroxybenzaldehyde yields phenantroimidazole derivatives. Indeed, these structurally robust polymers result in efficient, recyclable, heterogeneous photo-organocatalysts for the aza-Henry reaction (C-H functionalization) induced by visible-light irradiation. Copyright © 2020 American Chemical Society.
do Carmo Carreiras M, Ismaili L., Marco-Contelles J.
Bioorganic and Medicinal Chemistry Letters, vol. 30, nº 3 (2020)
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Current options for the treatment of Alzheimeŕs disease have been restricted to prescription of acetylcholinesterase inhibitors or N-methyl-D-aspartate receptor antagonist, memantine. Propargylamine-derived multi-target directed ligands, such as ladostigil, M30, ASS234 and contilisant, involve different pathways. Apart from acting as inhibitors of both cholinesterases and monoamine oxidases, they show improvement of cognitive impairment, antioxidant activities, enhancement of iron-chelating activities, protect against tau hyperphosphorylation, block metal-associated oxidative stress, regulate APP and Aβ expression processing by the non-amyloidogenic α-secretase pathway, suppress mitochondrial permeability transition pore opening, and coordinate protein kinase C signaling and Bcl-2 family proteins. Other hybrid propargylamine derivatives are also reported. © 2019 Elsevier Ltd
Capanni F, Muñoz-Arnanz J, Marsili L, Fossi M.C, Jiménez B.
Marine Pollution Bulletin, vol. 156 (2020)
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Bio-accumulation of high levels of persistent organic pollutants represent a serious conservation concern for Mediterranean marine odontocetes. In this study, blubber samples from 10 striped dolphins (Stenella coeruleoalba) stranded along the Italian coasts during 2015–2016 were analyzed. All specimens showed dl-PCBs > PBDEs ≫ PCDD/Fs. Median concentrations were 1820 ng/g l.w., 456 ng/g l.w. and 23.9 pg/g l.w., respectively. dl-PCBs accounted for 93.3\% of total TEQs. PBDE concentrations suggest that the Mediterranean basin may be considered a hotspot for organobromine compounds. OCDD did not represent the greatest contributor to PCDD/Fs profile, most likely due to a change in dioxin environmental sources in the last two-three decades. Despite international regulations, the present study emphasized that POP exposure levels in Mediterranean striped dolphins have not declined significantly in recent years. Toxicological and risk assessment studies on this sentinel species may provide an early indication of potential adverse health effects on Mediterranean ecosystems. © 2020 Elsevier Ltd
Toledano-Pinedo M, del Campo T.M, Tiemblo M, Fernández I, Almendros P
Organic Letters (2020)
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α,β-Unsaturated α′-alkoxy ketones have been prepared under mild conditions from allenes using water as the oxygen source and without the necessity of metals. The organocatalytic oxygenation-rearrangement sequence displays an exquisite chemo-, stereo-, and site-selectivity as well as good functional group compatibility. DFT calculations suggest that stabilizing noncovalent Se···O interactions may be responsible for the observed reactivity. © 2020 American Chemical Society.