Metal-Promoted Heterocyclization: A Heterosynthetic Approach to Face a Pandemic Crisis

The outbreak of SARS-CoV-2 has drastically changed our everyday life and the life of scientists from all over the world. In the last year, the scientific community has faced this worldwide threat using any tool available in order to find an effective response. The recent formulation, production, and ongoing administration of vaccines represent a starting point in the battle against SARS-CoV-2, but they cannot be the only aid available. In this regard, the use of drugs capable to mitigate and fight the virus is a crucial aspect of the pharmacological strategy. Among the plethora of approved drugs, a consistent element is a heterocyclic framework inside its skeleton. Heterocycles have played a pivotal role for decades in the pharmaceutical industry due to their high bioactivity derived from anticancer, antiviral, and anti-inflammatory capabilities. In this context, the development of new performing and sustainable synthetic strategies to obtain heterocyclic molecules has become a key focus of scientists. In this review, we present the recent trends in metal-promoted heterocyclization, and we focus our attention on the construction of heterocycles associated with the skeleton of drugs targeting SARS-CoV-2 coronavirus

Adotta un elemento

Adotta un elemento 2014 2015: Questa attività nasce dall’esigenza di introdurre la tavola periodica come un alfabeto da utilizzare per comporre le sostanze della materia che ci circonda, e non un astruso elenco di nomi e simboli completamente distaccati dalle sostanze che manipoliamo abitualmente. Di conseguenza dopo aver visitato le scuole con attività pratiche sugli elementi chimici e sulle loro proprietà, si desidera con questa attività seminare la curiosità su alcuni aspetti che per motivi di tempo non possono essere valutati nella attività “viaggio attraverso gli elementi chimici”. Il web con numerosi siti di interesse chimico, risulta essere un ottima risorsa dal punto di vista di informazioni e facilmente fruibile da parte degli studenti più interessati. Siti come ad esempio: http://it.wikipedia.org/wiki/Tavola_periodica_degli_elementi, http://chemistry.about.com/od/everydaychemistry/tp/Chemistry-In-Daily-Life.htm, http://www.textbooksonline.tn.nic.in/Books/Std08/Std08-MSSS-I-EM-S-3.pdf, http://www.minerva.unito.it/Chimica&Industria/SistemaPeriodico/TabellaSemplice.htm, possono essere un buon spunto per iniziare un viaggio di conoscenza su elementi noti ma dalle inaspettate proprietà e presenti ad esempio come principio attivo in farmaci, in materiali ad alte prestazioni, in additivi in alimenti, in enzimi dalle fondamentali attività negli organismi viventi e così via. E’ ben chiara la trasversalità dell’attività che porterà lo studente ad attraversare le discipline di fisica, chimica e biologia in maniera elastica mettendo in relazione principi di base e conoscenze generali. Questa attività ha lo scopo di presentare gli elementi e il loro impiego da un punto di vista nuovo, un punto di vista che metta in luce l’importanza della chimica e della sua ricaduta in termini di sviluppo tecnologico e umano. Come esempio, si pensi a tutto lo sviluppo dell’elettronica e all’importante sviluppo civile e tecnologico dovuta alla scoperta delle proprietà semiconduttrici del Silicio e alla messa a punto del metodo Czochralski (http://it.wikipedia.org/wiki/Processo_Czochralski) per la purificazione e la costruzione di monocristalli di Silicio. Questa attività prevede: i) la preparazione di un elaborato di almeno 8 pagine (carattere a scelta, corpo 12, interlinea 1.5) e di una presentazione PPT e/o multimediale, corredati da eventuali semplici esperimenti pratici inediti rispetto all’attività 1) su un elemento della tavola periodica. L’elaborato tratterà un solo elemento chimico. ii) L’attività deve essere presentata da un singolo studente che sia motivato nell’approfondimento dello studio della chimica. Ad ogni studente viene assegnato in via esclusiva un elemento della tavola periodica all’eventuale fine di ricostruire una tavola periodica virtuale. iii) L’elaborato dovrà contenere un breve cappello introduttivo sulle caratteristiche generali dell’elemento e su note storiche sulla sua scoperta e approfondire gli aspetti applicativi tecnologici, farmacologici e merceologici dell’elemento e/o dei suoi derivati. iv) I riferimenti bibliografici e le fonti usate nella preparazione dell’elaborato devono essere citate alla fine dell’elaborato. v) Per la preparazione della presentazione metodi comunicativi alternativi e innovativi sono benvenuti tali come fumetti, video ed esperimenti inediti. vi) Il lavoro dovrà essere prettamente individuale, coadiuvato dai docenti delle Scuole Secondarie vii) Si prevede una giornata conclusiva negli ultimi giorni di maggio 2013 dove gli studenti presenteranno il loro studio. viii) L’acquisizione dei CFU da parte dello studente concorrente può essere convalidata attenendosi alle procedure del regolamento di Scuola e di Ateneo. L’adozione di un elemento da parte di uno studente dovrebbe essere fatta durante o subito dopo la attività sulla tavola periodica. L’adesione deve essere comunicata al docente referente compilando il sotto riportato modulo che a sua volta lo comunica a referente UNICAM [email protected]. Una commissione di docenti del corso di laurea in chimica valuterà gli elaborati degli studenti concorrenti. Questa attività è rivolta agli studenti particolarmente curiosi e attivi. L'attività si pone come obiettivi lo sviluppo di conoscenze nel campo degli elementi chimici, lo stimolo allo studio della materia e lo sviluppo di capacità comunicative. L'attività si articola su più fasi: i) la scelta di un elemento chimico, ii) la ricerca dei suoi aspetti chimici e fisici di base, iii) la ricerca su come questi aspetti cambino nei composti derivati dall'elemento. Il punto cruciale di questo studio riguarda l'individuazione dei prodotti con questi elementi che manipoliamo nella vita quotidiana. Classi coinvolte: Classi 4e e 5e. Tutti gli studenti curiosi sarebbe potenzialmente idonei per questa attività. Tuttavia si ritiene che alcune competenze utili per questa attività (come capacità comunicative sia orali che scritte, organizzazione dell’elaborato, capacità di sintesi) siano riscontrabili in studenti del 4 e 5 liceo scientifico e di scienze applicate. Calendario: Adozione dell’elemento entro fine febbraio 2015 Conferma adozione entro prima decina di marzo Consegna degli elaborati 20 aprile 2015 Upload degli elaborati approvati nel sito http://d7.unicam.it/plschimica Giornata finale con comunicazioni orali sull’elemento adottato alla fine di maggio (intorno al 20 maggio, mercoledì

CeCl3 catalyzed imino Diels-Alder reactions: hydrated vs anhydrous

Aza-Diels-Alder reaction is a straightforward way to synthesize useful nitrogen containing heterocyclic structures.1 In particular, the known reaction between imines and Danishefsky’s diene has proved to be an excellent way to obtain the 1,2-substituted-2,3-dihydropyridinone scaffold, widely present in bioactive small molecules and versatile building block for the synthesis of more complex structures.2 The reaction of Danishefsky’s diene with aromatic imines has been widely studied in last years, anyway less examples of the same reaction involving imines derived from aliphatic amines or aldehydes are present. For this reason the possibility to extend the potentiality of this reaction performing it on a large variety of imines was studied, under the Lewis acid promoting system CeCl3.7H2O/CuI, previously applied with success3 in many other synthetic methodologies. Imines 3 were prepared by direct condensation of aliphatic or aromatic amines and aldehydes and then the diene was added together with the catalyst, obtaining dihydropyridinones 4 with good to excellent yields in short reaction times. To extend the scope of this work, also imines derived from aminoacids were tested as dienophiles. The only moderate diastereoselectivity and the long time needed with some homochiral dienophiles prompted us to have a deeper insight into the mechanism, with the conclusion that the reaction proceed also through a slower competitive Mannich-Michael pathway, favoured by the presence of water in the catalyst. 1) Buonora, P.; Olsen, J.-C.; Oh, T. Tetrahedron 2001, 57, 6099-6138. 2) Cant, A. A.; Sutherland, A. Synthesis 2012, 44, 1935-1950. 3) Bartoli, G.; Marcantoni, E.; Marcolini, M.; Sambri, L. Chem. Rev. 2010, 110, 6104-6143

The non-proteic extrusive secondary metabolites in ciliated protists

The non-proteic extrusive secondary metabolites in ciliated protists F. Buonanno1, A. Anesi2, G. Guella2, E. Marcantoni3, S. Giorgi3, C. Ortenzi1 1Laboratory of Protistology and Biology Education, University of Macerata, 62100 Macerata, Italy 2Bioorganic Chemistry Laboratory, Department of Physics, University of Trento, 38050 Povo, Trento, Italy 3School of Sciences and Technologies, Section of Chemistry, University of Camerino, 62032 Camerino, Macerata, Italy Extrusomes are membrane-bound ejectable organelles widely distributed in protists. They are usually localized in the cell cortex and attached to the cell membrane, and they are able to discharge their contents to the outside of the cell in response to mechanical or chemical stimuli. Notably, cells that discharge their extrusomes remains intact and functional. The chemical nature of protists\u2019 extrusive compounds characterized to date is extremely variable, including proteins, carbohydrates, lipids, and dozens of additional classes of secondary metabolites. However an increasing set of data are now available for particular group of protists, the ciliated protozoa. Many of non-proteic extrusive secondary metabolites in ciliates function for chemical offense or defense in prey-predator interactions against unicellular or/and multicellular organisms. It is worthy of note that at least some of these secondary metabolites have been demonstrated to show antibiotic, anti-cancer and pro-apoptotic properties in addition to their physiological functions. Among these compounds, euplotin C produced by the ciliate Euplotes crassus, and climacostol produced by Climacostomum virens, have been shown to activate programmed cell death by impairing mitochondrial membrane potential and inducing ROS generation in mammalian tumor cell lines. Interestingly, an antimicrobial activity against Gram-positive bacteria and fungal pathogens was also demonstrated for climacostol. Overall, in addition to the understanding of their physiological and ecological functions, the study of non-proteic secondary metabolites of ciliated protozoa may set the basis for the development of a novel series of antitumor and antimicrobial agents

An Efficient Catalytic Method for Regioselective Sulfenylation of Electron-rich Aza-aromatics at RoomTtemperature

Electron-rich aza-aromatic compounds such as indoles and pyrroles represent systems of particular interest and importance in organic chemistry. An useful methodology for regioselective direct introduction of sulfenyl group on electron-rich aza-aromatics through S-alkyl and S-arylthiophthalimides as sulfenylating agents is described. Catalytic amounts of CeCl3.7H2O-NaI system are crucial to the promotion of this regioselective carbon-sulfur bond-forming Friedel-Crafts reaction. The reaction occurred in mild conditions and the products were obtained in good to excellent yields. Due to the large importance of functionalized indoles among natural compounds and pharmaceutical products, the methodology represents an efficient preparation of sulfenyl aza-aromatics, which are useful intermediates for important organic transformations

An Efficient Lewis Acid Catalyzed Povarov Reaction for the One-Pot Stereocontrolled Synthesis of Polyfunctionalized Tetrahydroquinolines

An easy and efficient synthetic methodology for the one-pot stereocontrolled synthesis of tetrahydroquinolines through Lewis acid activated Povarov reaction is described. The protocol takes advantage of the very cheap, easy to handle, and environmentally friendly cerium trichloride as catalyst and allows to obtain either the anti- or the syn-isomer of the final tetrahydroquinoline with good selectivity, by performing the reaction in solvent or solventless conditions. The scope of the reaction is expanded to the one-pot synthesis of N-alkyltetrahydroquinolines through a very efficient iminium-Povarov approach. A deeper insight on the reaction system was provided by the study on the side reactions occurring in the reaction conditions and on the nature of the stereoselectivity

DNA binding and oxidative DNA damage induced by climacostol\u2013copper(II) complexes: Implications for anticancer properties

Climacostol is a natural toxin isolated from the freshwater ciliated protozoan Climacostomum virens and belongs to the group of resorcinolic lipids. Climacostol exerts a potent antimicrobial activity against a panel of bacterial and fungal pathogens. In addition it inhibits the growth of tumor cell lines in a dose-dependent manner by inducing programmed cell death via intrinsic pathway. In this work, we investigated the possibility that climacostol exerts a prooxidant effect, inducing plasmid DNA strand breakage and eukaryotic DNA damage in presence of Cu(II) ions. Inhibition of DNA breakage using SOD, catalase and neocuproine confirmed the involvement of reactive oxygen species and Cu(I) ions in the DNA damage. UV\u2013visible absorption changes and mass spectrometric analysis identified a product of reaction as a deprotonated form of climacostol. Study of the interaction with DNA, using fluorescence spectroscopic techniques, showed that climacostol binds with DNA. Given the structure\u2013activity relationship of this compound and the mechanism of its prooxidant effect, we propose that the Cu(II)-mediated oxidative DNA damage by climacostol could explain its antimicrobial and antiproliferative activity

An efficient synthesis of bio-based Poly(urethane-acrylate) by SiO2-Supported CeCl3·7H2O–NaI as recyclable Catalyst

Poly(urethane-acrylates) (PUAs) are UV-curable resins used for biomedical applications, coatings, adhesives, and many others. Their syntheses usually involve the use of aromatic diisocyanates and polyols coming from fossil-based resources, in the presence of tin-based catalysts, which present a very well-known toxicity. In the last years the increase of environmental and economic issues related to the depletion of limited sources, the increase of greenhouse gas emissions, the release of toxic degradation compounds and the catalyst contamination has shifted the attention toward more sustainable solutions. In this study a low-impact, sustainable and efficient procedure for the synthesis of bio-based PUA promoted by solid supported CeCl3·7H2O–NaI/SiO2 was developed. This catalytic system provides the target compounds with good monomer conversion and molecular weights and allow the synthesis under heterogeneous conditions as main advantage, with the final recovery of the catalyst. We also confirmed its rapid separation, stability, and efficient recycling of the catalyst, obtaining comparable results over a seven reactions cycles. The goodness of the polymerization process under heterogeneous condition was confirmed by chemical and thermal characterizations

Optimization of left ventricular pacing site plus multipoint pacing improves remodeling and clinical response to cardiac resynchronization therapy at 1 year

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