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A convenient and cost-effective method for selective deuteration of rutin using biologically compatible bases and D2O both as a deuterium source and a solvent is herein reported. The protocol is benign and inexpensive affording good results in very mild conditions allowing to reduce the required amount of deuterium oxide. The position of the C-H/C-D exchange and the level of deuteration can be conveniently followed by 1H-NMR.

A simple and efficient method to convert elemental selenium into alkali metal diselenide was developed. The use of selenium and metal borohydride in a molar ratio of 1 to 0.125 in the presence of base, under “on water” conditions and ultrasound activation permitted the reduction of Se into Se22- to be completed within minutes. Thus obtained metal diselenide aqueous solution was then used in the multigram scale synthesis of 2,2’-diselenobis(benzoic acid) (DSBA) a valuable building block for the development of diverse and pivotal selenorganic compounds.

The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (Mpro) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent Mpro inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold. In particular, we report here a new synthetic method to prepare previously inaccessible C-8 seleno-quercetin derivatives. By screening a small library of flavonols and flavone derivatives, we observed that some compounds inhibit the protease activity in vitro. For the first time, we demonstrate that quercetin (1) and 8-(p-tolylselenyl)quercetin (2d) block SARS-CoV-2 replication in infected cells at non-toxic concentrations, with an IC50 of 192 μM and 8 μM, respectively. Based on docking experiments driven by experimental evidence, we propose a non-covalent mechanism for Mpro inhibition in which a hydrogen bond between the selenium atom and Gln189 residue in the catalytic pocket could explain the higher Mpro activity of 2d and, as a result, its better antiviral profile, This work was supported by the University of Perugia “Fondo per la Ricerca di Base 2019”(C.S.); Fundación hna (to A.V.C. and O.A.); Miguel Servet Program from Instituto de Salud Carlos III (CPII13/00017 to O.A.); Fondo de Investigaciones Sanitarias from the Instituto de Salud Carlos III, and the European Union (ERDF/ESF, “Investing in your future”) (PI18/00349 to O.A. and an FIS Research Contract to L.C.L.); Spanish Ministry of Economy and Competitiveness (BFU2016-78232-P to A.V.C.); Spanish Ministry of Science, Innovation and Universities (FPI Predoctoral Research Contract BES-2017-080739 to D.O.A.); Diputación General de Aragón (Predoctoral Research Contract 2019 to A.J.A., “Protein Targets and Bioactive Compounds Group” E45_20R to A.V.C., “Digestive Pathology Group” B25_20R to O.A.); and Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001. FAPERGS, CNPq, and FINEP are acknowledged for financial support. CNPq is also acknowledged for fellowships to E.J.L. and D.A. This work was supported by the subsidy from the Polish Ministry of Science and Higher Education for research on the

Ebselent has been recently reported as the most efficient hinibitors of Sars-Cov-2 main protease (Mpro) thought the electrophilic covalent pro-oxidation of the reactive Cysteine 145. According to similar evidences in literature we can propose a general mechanism to explore a novel and promising application of mild organoselenium centered electrophiles in medicinal chemistry. New insights in the field of covalent and non-covalent inhibition of Mpro as well as the antiviral SARS-Cov2 activity of novel organoselenium compounds will be here discussed

New Ebselen-like derivatives resulted to be very strong in vitro inhibitors of SARS-CoV-2 main protease. We demonstrated that this activity mainly depends on the electrophilicity of the selenium atom that is considerably higher in the N-substituted 1,2- benzoselenazol-3(2H)-ones respect to the corresponding diselenides allowing it to be rapidly attached by free thiols affording sulfur-selenium intermediates that are further subjected to thiol exchange processes. This data paints a very complex scenario that requires us to consider Ebselen and Ebselen-like derivatives as potential electrophilic substrates for the several other free thiols present in the cell beside the target free cysteine. The sulfur selenium intermediates are milder electrophiles that could be theoretically implicated in both the detoxification process as well as in the final enzymatic inhibition. We here demonstrated that the in vitro inhibition activity is not fully reproduced in the prevention of viral replication in the cell-based assay. This indicates that the structure of the substituents introduced in the Ebselen scaffold is a crucial factor to control the reactivity of the selenated molecule in the network of thiol exchanges, as well as for molecular recognition of the targeted enzymatic cysteine. For this reason, an in-depth investigation is strongly desirable to better understand how to increase the activity and the selectivity of Ebselen derivatives overcoming the issues of the apparent PAINS-like role of Ebselen. Furthermore, besides the antiviral activity, thee selected compounds also showed a different ability to reduce the virus-induced cytopathic effect, indicating that other mechanisms could be implicated. One may consider here the well-known cytoprotective antioxidant activity of Ebselen and its derivatives.

A new eco-friendly and reliable methodology for the synthesis of 1,2,3,4-tetrahydroquinazolines is proposed. This simple protocol was tested for the continuous synthesis of a small library of 1,2,3,4-tetrahydroquinazoline derivatives demonstrating good versatility and applicability.

Mannich-type addition of 1,3-dicarbonyl compounds to (SS)-N-tert-butanesulfinyltrifluoroacetaldimine has been carried out under dramatically different conditions. The stereochemical outcome was quite different when the reaction was carried out under solvent-free conditions, at high temperature and without any catalyst or additive, compared with the DBU catalyzed reaction in dichloromethane solution at low temperature. Mechanistic aspects of the reaction under both the conditions are discussed. In this respect, vibrational (VCD) and electronic circular dichroism (ECD) and optical rotatory dispersion (ORD) experiments proved to be valuable tools for determining the absolute configurations of the reaction products.

A novel approach to synthesize hydroxy lactones using flow chemistry is reported. The system could be applied to a variety of functionalized alkenoic acids allowing the simple and eco-friendly generation of lactonic products within one hour (50 min). The reaction was optimized in terms of efficiency, productivity, resources and eco-sustainability using an integrated flow process assisted by in-line work-up and purification. In one example, the method was scaled to deliver 22 mmol of the product.

A simple, efficient, and selective oxidation under flow conditions of sulfides into their corresponding sulfoxides and sulfones is reported herein, using as a catalyst perselenic acid generated in situ by the oxidation of selenium (IV) oxide in a diluted aqueous solution of hydrogen peroxide as the final oxidant. The scope of the proposed methodology was investigated using aryl alkyl sulfides, aryl vinyl sulfides, and dialkyl sulfides as substrates, evidencing, in general, a good applicability. The scaled-up synthesis of (methylsulfonyl)benzene was also demonstrated, leading to its gram-scale preparation.

For a long time, the main biological activity of selenium derivatives was supposed to be connected to their toxicity and some exotic theories correlated historical events to the selenium poisoning. In 1285, Marco Polo, crossing the Shanxi Province of Western China, observed an unknown intoxication of the animals on his ships (loss of hair) that later was supposed to be due to selenosis and in 1860, a US Army surgeon documented the first selenium poisoning in livestock, suggesting a fascinating theory that the horse illness that slowed General Custer's Cavalry relief may have been due to selenium intoxication. Even if nowadays, several studies have confirmed that some disorders in animals and humans are consequence of selenium bioaccumulation it is also clear that selenium is fundamental for life having the role of essential micronutrient in mammals. As direct consequence of these prejudices the research in the field was particularly slow in the past and relegated to a small number of group in the world. Only recently the knowledge acquired in 200 years of basic research are finding applications in understanding of biological models involving selenoproteins, developing of new drugs, new functionalized materials and new catalytic protocols for green chemistry. This manuscript aims to be a celebrative tribute to the 200th "selenium birthday" presenting an overview of the contribute of our group in different field of this research, ranging from the development of new reagents for green chemistry and catalysis to the design and synthesis of novel molecules as anti-HIV and antimicrobial agents. We are strongly convinced that in the next future we can expect important discoveries from a research that produce thousand of new publications every year. Here we'll trace also where we are going to collecting some selected results recently obtained and presented by s number of our young students at 6th Workshop of the SeSRedCat Network in Wroclaw Poland 21-23 September 2017)

A general and efficient method for the selenium catalyzed cyclofunctionalization reaction of alkenoic acids and alkenols is presented. Hydrogen peroxide was used as the green oxidant and all the products were obtained in very good yields.

The selenium catalyzed oxidation by hydrogen peroxides was achieved for the synthesis of epoxides1. Our group recently developed the stereoselective synthesis of anti-1,2-diols passing through an epoxide intermediate2 and involving a perselenenic acid as actual catalyst of the whole process. Here we report the cyclofunctionalization of beta,gamma- and gamma,delta unsaturated acids, and alcohols. The stereoselectivity has been investigated starting from substrates containing additional chiral center in the α position as well as optically pure catalysts. All the reactions were carried out using 4 equivalents of hydrogen peroxides (30%) and diselenides as precatalysts without any organic solvents. High regio- and stereo-selectivity were obtained for almost all the substrates but unfortunately using optically pure diselenides only moderated enantiomeric excesses were obtained. The reaction conditions present important eco-friendly features (on water conditions, room temperature and pressure), generally affording high yields. - References - 1) Garcia-Marin,H; van der Toorn, J. C.; Mayoral, J. A.; Garcia, J. I. J. Mol. Catal 2011, 83-88 2) Santoro, S; Santi, C.; Sabatini, M.; Testaferri, L; Tiecco, M. Adv. Synth. Catal. 2008, 350, 2881-2884