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The stereoselective addition of ethyl acetate enolate to the C═N bond of N-tert-butylsulfinylimines has been investigated in depth. A significant effect of the LHMDS amount and the N-sulfinylimine nature on the stereoselectivity of the process was observed. Conditions were found where sulfinylimines of differently substituted salicylaldehydes derivatives, ethyl acetate, and LHMDS afforded the corresponding addition products as a single diastereomer in good yields. The developed protocol was successfully applied to the first stereoselective synthesis of differently substituted 4-amino-3,4-dihydrocoumarin derivatives. Computational models confirmed the prominent role of the ortho aryl substituent in the stereoselectivity of the process. A significant and selective cytotoxic activity against Glioblastoma Multiforme (GBM) cancer line has been determined for the noncyclic hydroxy ester derivative. Ministerio de Ciencia e Innovación PID2019-104767RB-I00 Junta de Andalucía US- 1381590, FQM-106

This work has been supported by Ministerio de Ciencia, Innovación y Universidades, Plan Estatal 2017-2020 Retos - Proyectos I + D + i (PID2019-104767RB-I00). MRGL also thanks Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (grants PI19/00589, PI19/01404, PI16/01842, PI17/00535 and GLD19/00100) for financial support. This work was supported by funds from MIUR Ministero dell’Istruzione, dell’Università della Ricerca Italiano, project PRIN 2017, ORIGINALE CHEMIAE in Antiviral Strategy—Origin and Modernization of Multi-Component Chemistry as a Source of Innovative Broad-Spectrum Antiviral Strategy (cod. 2017BMK8JR) and from Tuscany region, project Tuscany Antiviral Research Network -TUSCAVIR.NET (Bando Ricerca Salute 2018). We would like to thank Giulietta Venturi for making the ZIKV H/PF/2013 strain available for this study. This work has also been funded by the Fundación Séneca de la Región de Murcia under Project 20988/PI/18. This research was partially supported by the computer resources and the technical support provided by the supercomputing infrastructure of the NLHPC (ECM-02), Powered@NLHPC and the Extremadura Research Centre for Advanced Technologies (CETA − CIEMAT), funded by the European Regional Development Fund (ERDF). CETA − CIEMAT is part of CIEMAT and the Government of Spain. Authors thank CITIUS (Centro de Investigación, Tecnología e Innovación de la Universidad de Sevilla) for its important contribution in recording NMR and Mass spectra and in elemental analysis determination., Supplementary data to this article can be found online at https://doi.org/10.1016/j.bioorg.2023.106408, Since 2011 Direct Acting antivirals (DAAs) drugs targeting different non-structural (NS) viral proteins (NS3, NS5A or NS5B inhibitors) have been approved for clinical use in HCV therapies. However, currently there are not licensed therapeutics to treat Flavivirus infections and the only licensed DENV vaccine, Dengvaxia, is restricted to patients with preexisting DENV immunity. Similarly to NS5 polymerase, the NS3 catalytic region is evolutionarily conserved among the Flaviviridae family sharing strong structural similarity with other proteases belonging to this family and therefore is an attractive target for the development of pan-flavivirus therapeutics. In this work we present a library of 34 piperazine-derived small molecules as potential Flaviviridae NS3 protease inhibitors. The library was developed through a privileged structures-based design and then biologically screened using a live virus phenotypic assay to determine the half-maximal inhibitor concentration (IC50) of each compound against ZIKV and DENV. Two lead compounds, 42 and 44, with promising broad-spectrum activity against ZIKV (IC50 6.6 µM and 1.9 µM respectively) and DENV (IC50 6.7 µM and 1.4 µM respectively) and a good security profile were identified. Besides, molecular docking calculations were performed to provide insights about key interactions with residues in NS3 proteases’ active sites., Ministerio de Ciencia, Innovacion y Universidades, Plan Estatal 2017-2020 Retos-Proyectos I + D + i (PID2019-104767RB-I00), Spanish Government PI19/00589 PI19/01404 PI16/01842 PI17/00535 GLD19/00100, MIUR Ministero dell'Istruzione, dell'Universita della Ricerca Italiano, project PRIN 2017, ORIGINALE CHEMIAE in Antiviral Strategy-Origin and Modernization of Multi-Component Chemistry as a Source of Innovative Broad-Spectrum Antiviral Strategy 2017BMK8JR, Tuscany region, project Tuscany Antiviral Research Network-TUSCAVIR.NET (Bando Ricerca Salute 2018), Fundación Séneca 20988/PI/18, NLHPC ECM-02, European Commission

We report the fabrication of aqueous multimodal imaging nanocomposites based on superparamagnetic nanoparticles (MNPs) and two different sizes of photoluminescent upconverting nanoparticles (UCNPs). The controlled and simultaneous incorporation of both types of nanoparticles (NPs) was obtained by controlling the solvent composition and the addition rate of the destabilizing solvent. The magnetic properties of the MNPs remained unaltered after their encapsulation into the polymeric beads as shown by the T2 relaxivity measurements. The UCNPs maintain photoluminescent properties even when embedded with the MNPs into the polymer bead. Moreover, the light emitted by the magnetic and upconverting nanobeads (MUCNBs) under NIR excitation (λexc = 980 nm) was clearly observed through different thicknesses of agarose gel or through a mouse skin layer. The comparison with magnetic and luminescent nanobeads based on red-emitting quantum dots (QDs) demonstrated that while the QD-based beads show significant autofluorescence background from the skin, the signal obtained by the MUCNBs allows a decrease in this background. In summary, these results indicate that MUCNBs are good magnetic and optical probes for in vivo multimodal imaging sensors. U.S. Department of Energy DE-AC02-05CH11231 AIRC 14527 European Research Council 678109

Nowadays there is not an effective drug for the treatment of infections caused by human adenovirus (HAdV) which supposes a clinical challenge, especially for paediatric and immunosuppressed patients. Here, we describe the design, synthesis and biological evaluation as anti-adenovirus agents of a new library (57 compounds) of diester, monoester and triazole derivatives based on 3-amino-1,2-propanediol skeleton. Seven compounds (17, 20, 26, 34, 44, 60 and 66) were selected based on their high anti-HAdV activity at low micromolar concentration (IC50 from 2.47 to 5.75 µM) and low cytotoxicity (CC50 from 28.70 to >200 µM). In addition, our mechanistic assays revealed that compounds 20 and 44 might be targeting specifically the HAdV DNA replication process, and compound 66 would be targeting HAdV E1A mRNA transcription. For compounds 17, 20, 34 and 60, the mechanism of action seems to be associated with later steps after HAdV DNA replication., This work has been supported by Ministerio de Ciencia, Innovación y Universidades, Plan Estatal 2017-2020 Retos - Proyectos I + D + i (PID2019-104767RB-I00); Ministerio de Economía y Competitividad, Plan Nacional I + D + i 2013-2016, Retos-Proyectos (CTQ2016-78580-C2-2-R); Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Development Regional Fund “A way to achieve Europe”, the Instituto de Salud Carlos III, Proyectos de Investigación en Salud (PI17/01055; PI18/01191) and Proyectos de Desarrollo Tecnológico en Salud (DTS17/00130), the Spanish Adenovirus Network (AdenoNet, BIO2015/68990-REDT), and the program “Nicolás Monardes” (C-0059-2018), Servicio Andaluz de Salud, Junta de Andalucía.

A new family of sulfinamide/sulfoxide derivatives was synthesized as chiral bidentate ligands by stereoselective additions of methylsulfinyl carbanions to N-tert-butylsulfinylimines. The new ligands, with C1, pseudo-meso, and pseudo-C2 symmetries, were successfully assayed in Rh-catalyzed additions of arylboronic acids to activated ketones. The sterically dissymmetric C1 ligand (RS,SC,RS)-N-[1-(phenylsulfinyl)-3-methylbut-2-yl] tert-butylsulfinamide turned out to be the optimal one, allowing the 1,4-additions of diverse arylboronic acids, on different α,β-unsaturated cyclic ketones with high chemical yields and enantioselectivities up to >99% ee. Ministerio de Economía y Competitividad (Grant CTQ2016-78580-C2-2R)

Metal-free catalysis was successfully applied to polymerize ω-pentadecalactone (PDL) by ring-opening polymerization (ROP) using several amino-ended initiators, namely hexylamine, allylamine and O,O′-bis(3-aminopropyl)diethylene glycol. This polymerization method was suitable to prepare telechelic polyesters carrying functional-end groups. The technique was then extended to the synthesis of block copolymers by ROP of PDL using bisamino-ended poly(ethylene glycol) (Mn = 2600) as macroinitiator. PPDLx-PEG56-PPDLx triblock copolymers with Mn ranging between ∼4000 and ∼90,000 g ·mol−1 were synthesized and extensively characterized by NMR, DSC, TGA and XRD. The amphiphilic copolymers thus produced were demonstrated to be able to self-assemble in nanoparticles with average diameters of ∼100–200 nm and morphologies highly depending on blocks lengths. The described synthetic route distinguishes in providing “clean” amphiphilic copolymers, which are attractive candidates for biomedical applications. Ministerio de Economía y Competitividad MAT-2016- 77345-CO3-01, MAT-2016-77345-CO3-02

Ionic coupling of bacterial poly(γ-glutamic acid) (PGGA) with alkyltrimethylphosphonium surfactants is reported to render comb-like PGGA complexes with a biphasic-layered structure displaying periodicity at the nanoscopic scale. In this work, nanocomposites made of PGGA and montmorillonite, and covering a wide variety of compositions, are prepared by using either dodecyl- or eicosyl-trimethylphosphonium surfactant as a third component with a double purpose, that is, ionic complexation of PGGA and organo-modification of the nanoclay. Thermogravimetric analysis ascertains the compositions of these three-component nanocomposites and evidences their excellent thermal stability. The nanocomposite structure with PGGA and clay more or less intercalated according to composition and thermal history is evidenced by both X-ray diffraction and transmission electron microscopy. Simultaneous thermal SAXS/WAXS analysis at real time reveals extensive intermixing of the two phases that become notably enhanced by heating treatment. Thermal transition characteristics of the surfactant–PGGA complex are not significantly altered in the nanocomposites, but elastic moduli and strength to yield are found to increase proportionally to the content of clay. Ministerio de Ciencia, Innovación y Universidades de España (MICINN)-MAT2016-77345-C3-1-P Agencia de Gestión de Ayudas Universitarias y de Investigación de Barcelona-AGAUR 2009SGR1469

The capacity of redox D-mannitol-based polyurethanes to modulate the glutathione response under physiological conditions, as well as their effectiveness for sustained and site-specific drug release in the gastrointestinal tract (GIT), have been demonstrated in previous studies. Based on those promising results, our attention has now been drawn towards hydrolytic degradation processes at 37 °C and different pH values, from acidic to basic conditions, as in the GIT. For that, two sets of branched and linear D-mannitol-based polyurethanes containing disulfide bonds have been synthesized, which has been possible depending on the starting D-mannitol-derived monomer. Thus 3,4-O-isopropylidene-D-mannitol, having two secondary hydroxyl groups in addition to the two primary hydroxyl groups, afforded polyurethanes with a certain degree of branching. In contrast, 2,4:3,5-di-O-isopropylidene-D-mannitol and 2,3:4,5-di-O-isopropylidene-D-mannitol, lacking secondary hydroxyl groups, led to linear polyurethanes. Removal of the O-isopropylidene protecting groups resulted in more-hydrophilic materials. As in glutathione-mediated degradation, the branched polyurethanes presented enhanced degradation under physiological conditions, proportional to the content of D-mannitol, whereas linear polyurethanes were degraded slowly, and pH 8 and 10 were required. Ministerio de Economía y Competitividad MAT2012- 38044C03-01, MAT2016-77345-C3-2-P Junta de Andalucía FQM-1563

Sulforaphane (SFN), a phytochemical isolated from broccoli, is an important antitumoral compound with additional beneficial effect on other important diseases. However, the chemical instability of SFN has hampered its clinical use. In order to circumvent this problem, we report the first comparative study on the inclusion complexes of SFN and SFN homologues with different cyclodextrins by NMR spectroscopy. From this study it has been shown that α-CD is the most indicated cyclodextrin for the stabilization of SFN and SFN homologues, and that the highest affinity constant is that of the isothiocyanate obtained from the wasabi. Furthermore, the study of the inclusion complexes of α-CD and the non-natural SFN and analogues with S absolute configuration at sulfur shows for the first time that α-CD is able to discriminate between the two enantiomers, with the natural R enantiomers forming the inclusion complexes with higher affinity., This work was supported by the Ministerio de Economía y Competitividad (grants No. CTQ2016-78580-C2-1-R, and CTQ2016-78580-C2-2-R), the Junta de Andalucía (P11-FQM-8046), and Evgen Pharma.

The e ffi cient, controlled polymerization of a batch of new poly(hydroxyethyl methacrylate- co -furfuryl methacrylate)s, [poly(HEMA- co -FMA)], of various compositions was achieved using atom transfer radical polymerization (ATRP) in methanol. When the FMA composition did not exceed the 10 mol% ratio, the evolution of molecular weight with conversion was linear, and polydispersities were around 1.1 for polymerization reactions at 15 C and around 1.3 – 1.4 at 25 C, indicating good control over the polymerization process. HEMA-based hydrogels were obtained by means of the Diels – Alder reaction between poly(HEMA- co -FMA) and an hydrophilic bisdienophile. Geli fi cation was monitored by di ff usion- fi ltered 1 H NMR and solution 1 H NMR spectroscopy. Modulated temperature di ff erential scanning calorimetry (MTDSC) suggests the thermo-reversibility of the Diels – Alder coupling reaction of HEMA polymeric networks. Rheological studies showed that the linear viscoelasticity functions of hydrogels were in fl uenced by the chemical composition

Trypanosomiasis and leishmaniasis keep being a real challenge for health and development of African countries. Existing treatments have considerable side effects and increase resistance of the parasites. We have measured antitrypanosomal and antileishmanial activity of natural phenols, tyrosol (TYR) and hydroxytyrosol (HT) and several of their esters and metabolites. We found significant IC50 values against Trypanosoma brucei for HT decanoate ester and HT dodecanoate ester (0.6 and 0.36 μM, respectively). This represents a large increase in activity with respect to HT (79 and 132 fold, respectively). Moreover, both compounds displayed a high selectivity index against MRC-5, a non-tumoral human cell line (118 and 106, respectively). Then, we synthesized a focused library of compounds to explore structure-activity. We found the ether and thiourea analogs of HT decanoate ester and HT dodecanoate ester also showed IC50 values against T. brucei in the low micromolar range. In conclusion, the di-ortho phenolic ring and medium size alkyl chain are essential for activity whereas the nature of the chemical bond among them seems less important., We gratefully acknowledge to Junta de Andalucía (Grant No. FQM-7316 (JCM), BIO-1786 (JMPV), CTS-7282 (FG)) and Spanish Ministry of Economy and Competitiveness (Grant No. SAF2011-28215 (JMPV) and SAF2012-34267 (FG)) for financial support.

Resveratrol (RES) is a natural polyphenol with relevant and varied biological activity. However, its low bioavailability and rapid metabolism to its glucuronate and sulfate conjugates has opened a debate on the mechanisms underlying its bioactivity. RES prodrugs are being developed to overcome these problems. We have synthesized a series of RES prodrugs and RES sulfate metabolites (RES-S) and evaluated their biological activities. RES glucosylated prodrugs (RES-Glc) were more cytotoxic in HT-29 and MCF-7 cells than RES itself whereas RES-S showed similar or higher cytotoxicity than RES. VEGF production was decreased by RES-Glc, and RES-disulfate (RES-diS) diminished it even more than RES. Finally, RES-Glc and RES-diS inhibited hTERT gene expression to a higher extent than RES. In conclusion, resveratrol prodrugs are promising candidates as anticancer drugs. In addition, RES-S showed distinct biological activity, thus indicating they are not simply RES reservoirs., Financial support has been granted by the Spanish Government (Ministerio de Economía y Competitividad, projects CTQ2011–27560 and CTQ2012–35360), by the Consellería d'Empresa, Universitat i Ciencia de la Generalitat Valenciana (projects PROMETEO/2013/027) and by the Universitat Jaume I (project PI‐1B‐2011–37).

Reported is the synthesis of a number of diastereomerically pure cationic Rh(i)-complexes I starting from phosphinite thioglycosides. These complexes were used in the asymmetric hydrosilylation of prochiral ketones. The reactivity and enantioselectivity of the reaction was shown to be dependent on the pyranose ring, the substituent at the sulfur atom, the hydroxylic protective groups and most significantly on the alkene co-ligand Ministerio de Ciencia e Innovación CTQ2010-21755-CO2-00 Junta de Andalucía P07-FQM-2774

In the present work, we demonstrate the preparation of chitosan-based composites as vehicles of the natural occurring multi-drug resveratrol (RES). Such systems are endowed with potential therapeutic effects on inflammatory bowel diseases (IBD), such as Crohn&rsquo, s disease (CD) and ulcerative colitis, through the sustained colonic release of RES from long-lasting mucoadhesive drug depots. The loading of RES into nanoparticles (NPs) was optimized regarding two independent variables: RES/polymer ratio, and temperature. Twenty experiments were carried out and a Box&ndash, Behnken experimental design was used to evaluate the significance of these independent variables related to encapsulation efficiency (EE). The enhanced RES EE values were achieved in 24 h at 39 &deg, C and at RES/polymer ratio of 0.75:1 w/w. Sizes and polydispersities of the optimized NPs were studied by dynamic light scattering (DLS). Chitosan (CTS) dispersions containing the RES-loaded NPs were ionically gelled with tricarballylic acid to yield CTS-NPs composites. Macro- and microscopic features (morphology and porosity studied by SEM and spreadability), thermal stability (studied by TGA), and release kinetics of the RES-loaded CTS-NPs were investigated. Release patterns in simulated colon conditions for 48 h displayed significant differences between the NPs (final cumulative drug release: 79&ndash, 81%), and the CTS-NPs composites (29&ndash, 34%).

The preparation of a new type of derivatives of the naturally occurring antioxidant hydroxytyrosol is reported. Hydroxytyrosyl alkyl ethers were obtained in high yield by a three-step procedure starting from hydroxytyrosol isolated from olive oil waste waters. Preliminary results obtained by the Rancimat method have shown that these derivatives retain the high protective capacity of free hydroxytyrosol., We thank the Ministerio de Educación y Ciencia of Spain for financial support (grant no. AGL2007-66373).

A detailed study on the diastereoselective oxidation of 1-thio-β-D-glucopyranosides is reported. It has been shown that the sense and the degree of stereochemical outcome of the oxidation are highly dependent on the substituent of the sulfur and on the protective group of the C2–OH. In the case of thioglycosides with a bulky aglycone, the mesylation of C2–OH has a significant effect on the stereochemical outcome of the oxidation, affording the usually less favoured RS sulfoxide as a single diastereoisomer. The absolute configuration of the final sulfinyl glycosides was ascertained by NMR analysis and corroborated by X-ray crystallography.

Reported is an enantiodivergent approach for the synthesis of both enantiomers of sulforaphane (SFN) homologues with different chain lengths between the sulfinyl sulfur and the isothiocyanate groups and different substituents on the sulfinyl sulfur. The homologues were designed in order to unravel the effect of all the diversity elements included in sulforaphane's structure. The key step of the approach is the diastereoselective synthesis of both sulfinate ester epimers at sulfur, using as single chiral auxiliary the sugar derived diacetone-d-glucose. The approach allows the first synthesis of both enantiomers of 5-methylsulfinylpentyl isothiocyanate, and the biologically important 6-methylsulfinylhexyl isothiocyanate (6-HITC) found in Japanese horseradish, wasabi (Wasabia japonica). The ability of the synthesized compounds as inductors of phase II detoxifying enzymes has been studied by determining their ability to activate the cytoprotective transcription factor Nrf2. The cytotoxic activity of all the synthesized compounds against human lung adenocarcinoma (A549) and foetal lung fibroblasts (MRC-5) is also reported. Both enantiomers of sulforaphane and six homologues were obtained.The ability of the synthesized compounds to activate the Nrf2 is studied.The cytotoxic activity of the analogues against cancer and healthy cells is reported.

Physalis peruviana is a native plant from the South American Andes and is widely used in tra- ditional Colombian medicine of as an anti-inflam- matory medicinal plant, specifically the leaves, calyces, and small stems in poultice form. Pre- vious studies performed by our group on P. pe- ruviana calyces showed potent anti-inflamma- tory activity in an enriched fraction obtained from an ether total extract. The objective of the present study was to obtain and elucidate the ac- tive compounds from this fraction and evaluate their anti-inflammatory activity in vivo and in vi- tro. The enriched fraction of P. peruviana was pu- rified by several chromatographic methods to ob- tain an inseparable mixture of two new sucrose esters named peruviose A (1) and peruviose B (2). Structures of the new compounds were eluci- dated using spectroscopic methods and chemical transformations. The anti-inflammatory activity of the peruvioses mixture was evaluated using λ-carrageenan-induced paw edema in rats and lipopolysaccharide-activated peritoneal macro- phages. Results showed that the peruvioses did not produce side effects on the liver and kidneys and significantly attenuated the inflammation in- duced by λ-carrageenan in a dosage-dependent manner, probably due to an inhibition of nitric oxide and prostaglandin E2, which was demon- strated in vitro. To our knowledge, this is the first report of the presence of sucrose esters in P. pe- ruviana that showed a potent anti-inflammatory effect. These results suggest the potential of su- crose esters from the Physalis genus as a novel natural alternative to treat inflammatory diseases.

Quadruplex DNA structures are attracting an enormous interest in many areas of chemistry, ranging from chemical biology, supramolecular chemistry to nanoscience. We have prepared carbohydrate-DNA conjugates containing the oligonucleotide sequences of G-quadruplexes (thrombin binding aptamer (TBA) and human telomere (TEL)), measured their thermal stability and studied their structure in solution by using NMR and molecular dynamics. The solution structure of a fucose-TBA conjugate shows stacking interactions between the carbohydrate and the DNA G-tetrad in addition to hydrogen bonding and hydrophobic contacts. We have also shown that attaching carbohydrates at the 5′-end of a quadruplex telomeric sequence can alter its folding topology. These results suggest the possibility of modulating the folding of the G-quadruplex by linking carbohydrates and have clear implications in molecular recognition and the design of new G-quadruplex ligands. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim., We thank the MICINN (grants CTQ2009–13705, CTQ2010–20451, CTQ2010–21567-C02–02), EU COST project MP0802, Generalitat de Catalunya (2009/SGR/208), and Instituto de Salud Carlos III (CIBERBNN, CB06 01 0019) for financial support. IGP and RL thank CSIC for a JAE contract. EVC thanks the Ministry of Education for an FPU doctoral fellowship.

Reported is an efficient approach to the synthesis of water-soluble proline-coated gold nanoparticles through a place exchange reaction between pentanethiolate stabilized gold nanoparticles and a proline-tethered amphiphilic thiol. Preliminary studies show that the nanocatalyst is highly active in an enamine type aldolisation leading to the desired product with nearly perfect diastereoselectivity and enantioselectivity using water as an innocuous solvent Ministerio de Economía y Competitividad CTQ2010-21755-CO2-00 Junta de Andalucía P07-FQM-2774

2,4:3,5-Di-O-methylene-D-glucitol (Glux-diol) and dimethyl 2,4:3,5-di-O-methylene-D-glucarate (Glux-diester) have been copolymerized with ethylene glycol and dimethyl terephthalate by polycondensation in the bulk to produce PET copolyesters as well as their respective homopolyesters. These sugar-based bicyclic monomers were synthesized from 1,5-D-gluconolactone, a commercially accessible compound derived from D-glucose. The PET copolyesters with either the diol or the diacid counterpart partially replaced by Glux had molecular weights in the 20 000–40 000 range and a random microstructure, and they were stable well above 300 o C. The PET copolyesters containing more than 10–15% of sugar-based units were amorphous while those displaying crystallinity were observed to crystallize from the melt at much lower rates than PET. The glass transition temperature of PET dramatically increased with the incorporation of Glux, whichever unit, diol or diacid, was replaced, but the enhancing effect was stronger in the former case. A preliminary evaluation of the mechanical behaviour of these copolyesters indicated that the genuine properties of PET were not substantially impoverished by the insertion of Glux. Compared to PET, the copolyesters exhibited a higher hydrolysis rate and an appreciable susceptibility towards biodegradation. The homopolyesters made of these sugar-based monomers could not be obtained with high enough molecular weights so as to be comparatively evaluated with copolyesters. Ministerio de Economía y Competitividad MAT2009-14053-C02 AGAUR 2009SGR1469

Oligoribonucleotide conjugates carrying apolar carbohydrates at the 5′-end and the corresponding siRNA duplexes have been prepared using phosphoramidite chemistry. All the carbohydrate-siRNA derivatives were compatible with RNA interference machinery if transfected with oligofectamine. In the absence of a transfection agent, some of them exerted certain reduction of gene expression. Double-tailed permethylated glucose conjugated to siRNA through a long spacer inhibited gene expression up to 26% compared to the scrambled duplex. Such modifications contribute positively to the stability of oligoribonucleotides against 5′-exonuclease degradation., This study was supported by the Spanish Ministry of Economy and Competitiveness (grants CTQ2009-13705, CTQ2010-20541), Generalitat de Catalunya (2009/SGR/208). RL thanks CSIC for a JAE contract and EVC thanks Ministry of Education, Culture and Sports for a FPU grant. MT acknowledges a Juan de la Cierva contract (MICINN, Spain) for financial support.

5 páginas, 1 figura, 2 tablas, 5 esquemas., Phosphinite thioglycosides I for which a modular ­synthetic approach is reported, were found highly efficient catalyst precursors for palladium(0)-catalyzed asymmetric substitution. Both enantiomers of the allylated products have been obtained with high ee (up to 96%) using natural sugars as catalyst precursors., We thank the Dirección General de Investigación Científica y ­Técnica (grant No. PB BQU2003-00937 and CTQ2004-01057) and La Fundación Ramón Areces for financial support.

3 páginas, 3 figuras, 1 esquema., A strategy based on the utilization of neutral pyrene functionalized neoglycolipids I that interact with a CNT’s surface giving rise to biocompatible nanomaterials which are able to engage specific ligand-lectin interactions similar to glycoconjugates on the cell membrane is reported., Financial supports from the DGICyT (grant No. CTQ2006-15515-CO2-01 and CTQ2007-61185), the Junta de Andalucía (grant P06-FQM-01852 and P07-FQM-2774), the CNRS and CSIC (Egide Picasso 09543XA and PICS 2008 programmes) are gratefully acknowledged.

15 páginas, 8 figuras, 1 tabla, 3 esquemas., We have developed an efficient strategy for the non-covalent functionalization of multi-walled carbon nanotubes (MWCNTs) which allows a biomimetic presentation of carbohydrates on their surface by π-π stacking interactions. The strategy is based on the use of sugar-based amphiphiles functionalized with tetrabenzo[a,c,g,i]fluorene (Tbf), a polyaromatic compound with a topology that resembles a butterfly with open wings. The new carbohydrate-tethered Tbf amphiphiles have been synthesized in a straightforward manner using click chemistry. The reported method has been developed in order to improve the rather low ability of pyrene-based systems to exfoliate MWCNTs in water. By means of thermogravimetric analysis (TGA), ultraviolet (UV), infrared (IR), and fluorescence spectroscopies the interaction between MWCNTs and the Tbf group has been found to be stronger than those involving pyrene-based amphiphilic carbohydrates. The resulting aggregates with a multivalent sugar exposition on their surface are able to engage in specific ligand-lectin interactions similar to glycoconjugates on a cell membrane., This work was supported by the Ministerio de Ciencia e Innovación (grant No. CTQ2010-21755-CO2-00), the Junta de Andalucía (grant Nos. P06-FQM-01852 and P07-FQM-2774), the Centre National de la Recherche Scientifique (France) and the Consejo Superior de Investigaciones Científicas (Egide Picasso 09543XA and Projets Internationaux de Cooperation Scientifiques Program 2008-2010).

14 páginas, 4 figuras, 5 esquemas, 2 tablas., An efficient route to mixed phosphine / thioglycoside ligands type IV starting from glucose pentaacetate is reported. In only five steps the key epoxide 6 has been obtained in high yield and its structure determined by X-ray analysis. The ring opening of the tert-butyl 4,6-O-benzylidene-2,3-anhydro-1-thio-β-D-allopyranoside 6 with diphenylphosphinyl lithium afforded the desired ligand as a single diastereoisomer. The prepared compounds act as a bidentate ligands as shown by X-ray analysis of the Rh(I)-complex 12. Preliminary results on the behaviour of these ligands in Pd(0)-catalyzed allylic alkylation, and in Rh(I)-catalyzed enamide hydrogenation are also reported., We thank the Dirección General de Investigación Científica y Técnica (grant No. CTQ2006-15515-CO2-01 and CTQ2007-61185), the Junta de Andalucía (grant P06-FQM-01852 and P07-FQM-2774), la Fundación Ramón Areces for financial support, and Mr M. Rudkowski for performing preliminary experimental work.