Glycosyl sulfoxides have gained recognition in the total synthesis of complex oligosaccharides and as model substrates for dissecting the mechanisms involved. Reactions of these donors are usually performed under pre-activation conditions, but an experimentally more convenient single-step protocol has also been reported, whereby activation is performed in the presence of the acceptor alcohol; yet, the nature and prevalence of the reaction intermediates formed in this more complex scenario have comparatively received minimal attention. Herein, a systematic NMR-based study employing both 13C-labelled and unlabelled glycosyl sulfoxide donors for the detection and monitoring of marginally populated intermediates is reported. The results conclusively show that glycosyl triflates play a key role in these glycosylations despite the presence of the acceptor alcohol. Importantly, the formation of covalent donor/acceptor sulfonium adducts was identified as the main competing reaction, and thus a non-productive consumption of the acceptor that could limit the reaction yield was revealed. © 2020 Wiley-VCH GmbH

Dicationic ionic liquids are promising solvents for safe high performance Li-ion battery applications. In this work, we report on the synthesis and characterization of new electrolytes based on geminal dicationic pyrrolidinium and piperidinium bis(trifluoromethane)sulfonimide ionic liquids, where the two cations are linked by variable length oxyethylene chain spacers. All 1 M LiTFSI doped synthesized electrolytes are thermally stable up to 300 °C, and they exhibited remarkable electrochemical stability window up to 6.0 V vs. Li/Li+. Electrolytes were assembled with LiMn2O4 (LMO) spinel in lithium half-cells. Electrochemical cell performance in terms of cyclic voltammetry, rate capability and galvanostatic cycling studies have been studied at 60 °C. Results obtained indicate that both the cationic structure and the length of the oxyethylene chain spacer has a significant influence on the electrochemical performance of LMO-cells. The cell based on the pyrrolidinium electrolyte with the two cationic structures linked by two oxyethylene units exhibit the faster rate capability, with a capacity retention of 45\% at 5C, and the highest reversible capacity (ca. 80 mAhg-1). © 2019 Elsevier B.V.

This paper reports on the synthesis and characterization of novel dicationic ionic liquid electrolytes based on asymmetrical imidazolium-trialkylammonium ionic liquids. The results obtained indicate that the length of the alkyl chain attached to the nitrogen atom has a significant influence on the thermal and electrochemical properties of the electrolytes, as well as on parameters such as lithium ion coordination number and lithium ion transport number. All synthesized dicationic ionic liquids and the corresponding electrolytes are liquid at room temperature being thermally stable up to 300 °C; well above battery operation temperature. Room temperature ionic conductivities of the electrolytes are in the range of 0.8–7.2 × 10−5 S cm−1, with an electrochemical stability window of 1.5 V–5.0 V vs. Li/Li+. Synthesized electrolytes have been tested in Li half-cells using LiMn2O4 (LMO) spinel as cathode material. Cyclic voltammetry, rate capability and galvanostatic cycling studies at 60 °C have been performed. Again, the alkyl chain length attached to the nitrogen atom plays a significantly role in the electrochemical performance of the LMO cells. Among the cells studied, the one assembled with the electrolyte 1M LITFSI doped IMI1,6-TEA exhibits the best rate capability and the high cycling performance. © 2018 Elsevier Ltd

The synthesis and characterization of novel ionic liquid (ILs) based gel polymer electrolytes for application in sodium-ion (Na+) batteries is reported. It comprises a 0.2 M solution of NaN(CF3SO2)2 (sodium bis(trifluoromethylsulfonyl) imide) in mono and dicationic imidazolium-based ionic liquids immobilized in a poly(vinylidene fluoride)-hexafluoropropylene copolymer matrix. The membranes offer acceptable ionic conductivity, up to 2.2 × 10−4 S cm−1 at room temperature, with excellent thermal and electrochemical stabilities. The useful thermal stability reached up 150 °C and decomposition only starts at about 400 °C, while electrochemical stability window comprises from 1.5 V to 5.0 V vs. Na/Na+. Na+ transference values (tNa+) are in the range of 0.1 to 0.5, indicating a contribution of anionic transport (TFSI− anion) and component ions of ionic liquid to the total ionic conductivity. The nature of Na+ coordination and the formation of Na+-complexes were elucidated through Raman spectroscopy. The average number of TFSI coordinated to Na+ (n) allowed to know the contribution of the formed complexes in ionic mobility mechanism in the gel electrolytes. The effect of side chain length in oxyethylene-functionalized imidazolium mono and dicationic RTILs on both structural and electrochemical properties were discussed. Results obtained demonstrate promising characteristics of the membranes, being suitable candidates to be used in rechargeable sodium batteries. © 2017 Elsevier Ltd

Carbohydrate derivatives are useful chiral building blocks for the enantiomerically pure compound synthesis of an ample variety of compounds. In this chapter, we present an outline of our recent research on the synthesis of unsaturated carbohydrates and their applications as intermediates for the preparation of peptide-scaffold hybrids, functionalized heterocycles, and alkaloids through the use of the Claisen and Overman rearrangements as well as the sequential intramolecular azide-alkene cycloaddition/nitrogen extrusion; as exemplified in the first total synthesis of the pyrrolizidine alkaloid amphorogynine C. © 2016 by John Wiley & Sons, Inc. All rights reserved.

Two series of thiazolium bis(trifluoromethylsulfonyl)imide [NTf2] room temperature ionic liquids (RTILs) functionalized with oligo(oxyethylene)-chains have been synthesized in multigram scale and characterized. Their thermal properties and conductivity values have been determined. The increase in the number and length of the oligo(oxyethylene)-chains attached to the thiazolium ring resulted in lower values of ionic conductivity. © 2016 Elsevier Ltd

Synthesis of the core skeletons of the polycyclic alkaloids lycopodine and porantherine has been accomplished employing as a key step an Intramolecular Azide-Olefin Cycloaddition reaction (IAOC)/enamine addition/Mannich cascade reaction. Applying this methodology, the first synthesis of C15-desmethyl lycopodine has been developed. © 2016 Elsevier Ltd

In this review, we report an overview of some recent applications of ionic liquids in diverse organocatalyzed transformations such as, for example, the conjugate addition, Diels Alder and the aldol type reactions. Examples of ionic liquids acting both as catalyst (“nonsolvent applications”) and as reaction media are described. The interesting potential applications resulting of the merging of two such active research areas as ionic liquids and organocatalysis are only just starting to be explored by the synthetic organic chemists. © 2015 Bentham Science Publishers.

In this study, we explored the biocompatibility of Au nanoparticles (NPs) capped with peptide-biphenyl hybrid (PBH) ligands containing glycine (Gly), cysteine (Cys), tyrosine (Tyr), tryptophan (Trp) and methionine (Met) amino acids in the human hepatocellular carcinoma cell line Hep G2. Five AuNPs, Au[(Met)2B], Au[(Gly-Tyr-TrCys)2B], Au[(Met)2B], Au[(Gly-Tyr-TrCys)2B] and Au[(TrCys)2B], were synthesised. Physico-chemical and cytotoxic properties were thoroughly studied. Transmission electron micrographs showed isolated near-spherical nanoparticles with diameters of 1.5, 1.6, 2.3, 1.8 and 2.3 nm, respectively. Dynamic light scattering evidenced the high stability of suspensions in Milli-Q water and culture medium, particularly when supplemented with serum, showing in all cases a tendency to form agglomerates with diameters approximately 200 nm. In the cytotoxicity studies, interference caused by AuNPs with some typical cytotoxicity assays was demonstrated; thus, only data obtained from the resazurin based assay were used. After 48-h incubation, only concentrations ≥50 μg/ml exhibited cytotoxicity. Such doses were also responsible for an increase in reactive oxygen species (ROS). Some differences were observed among the studied NPs. Of particular importance is the AuNPs capped with the PBH ligand (Gly-Tyr-TrCys)2B showing remarkable stability in culture medium, even in the absence of serum. Moreover, these AuNPs have unique biological effects on Hep G2 cells while showing low toxicity. The production of ROS along with supporting optical microscopy images suggests cellular interaction/uptake of these particular AuNPs. Future research efforts should further test this hypothesis, as such interaction/uptake is highly relevant in drug delivery systems. © 2013 Connolly et al.

A cascade intramolecular azide-alkene 1,3-dipolar cycloaddition/Stork alkylation reaction has been developed for the synthesis of functionalized cyclic imines with a pyrroline and piperideine structures, employing readily available ω-azidodienes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A cascade intramolecular azide-alkene 1,3-dipolar cycloaddition/1,2 enamine and/or 1,4 enamine addition reaction sequence has been developed, and provides access to a variety of nitrogen containing heterocycles from readily available ω-azido alkenes. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The first total synthesis of the natural alkaloid amphorogynine C is reported (2.9 \% overall yield in 20 steps). The key steps include a Claisen-Johnson rearrangement and an intramolecular azide-olefin cycloaddition, followed by a reduction of the resulting imine. The construction of the pyrrolizidine skeleton was achieved by an alkoxide-mediatedlactone ring opening and subsequent cyclization of a conveniently functionalized bicyclic amine. Finally, the proposed structure of amphorogynine C was confirmed by single-crystal X-ray diffraction analysis. The first synthesis of the representative pyrrolizidine alkaloid amphorogynine C is described. The key step includes an intramolecular azide-olefin cycloaddition reaction. The proposed structure of the natural product was confirmed by single-crystal X-ray diffraction analysis. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gold nanoparticles were prepared using peptide-biphenyl hybrids (PBHs) as capping agents. AuNPs were characterized by different techniques including UV-Vis, TEM, EDX, FT-IR, elemental analysis, 1H NMR and 13C CP/MAS NMR spectroscopy. TEM analysis showed that AuNPs present diameters in the range of 1.8-3.7nm, depending on the structure and the amount of the capping PBH used. FT-IR spectroscopy and solid-state 13C NMR revealed that the carboxylic group of PBHs, especially in the case of the acid ligands, interacts with the gold surface (in the form of carboxylate). The results confirm that PBHs are excellent stabilizers of AuNPs, being one of the first examples on the use of peptidomimetics-gold hybrid materials. © 2011 Elsevier Inc.

Aims: Pifithrin α (PFTα), an inhibitor of the p53 protein, is regarded as a lead compound for cancer and neurodegenerative disease therapy. There is some evidence that this compound activates the aryl hydrocarbon receptor (AhR) in a complete independent way of the p53 inhibition and that it is easily converted to its condensation product pifithrin β (PFTβ). The aim of this study was to explore the ability of PFTα and of PFTβ to induce a variety of AhR mediated processes. Main methods: Computational analysis using quantum chemical calculations and chemical analysis have been used to study the conformation of the compounds as well as the cyclization reaction. The AhR mediated processes of these compounds have been studied in a rainbow trout cell line (RTG-2) and in a rat hepatoma cell line (H4IIE). Key findings: PFTα molecule could not take a planar conformation required for AhR activation whereas PFTβ showed a conformation similar to those of the prototypical AhR ligand β-naphthoflavone. In both cell lines, PFTα and PFTβ provoked different responses related with AhR activation. However, when cyclization of PFTα to PFTβ was hampered by acetylation of the exocyclic nitrogen, all these responses were not observed. These results lead to the conclusion that the activation of the AhR is probably caused by PFTβ instead of PFTα. Significance: Since PFTα is a promising compound for the development of new pharmaceuticals inhibiting p53, the chemical instability of this compound as well as the capacity of its transformation product should be taken into account. © 2011 Elsevier Inc.

A stereocontrolled synthesis of an unsaturated sugar bearing two amino groups (one of them masked as an azide), using an Overman rearrangement as key step, is described. This scaffold is used to prepare two peptides having aromatic fragments, which have shown activity as calpain inhibitors. © 2004 Elsevier Ltd. All rights reserved.

Calpain is a cysteine protease that is activated by Ca2+. The over-activation of calpain, which occurs on increasing Ca2+ concentration, causes a variety of diseases. This paper reports experimental results on the inhibition of calpain I (μ-calpain) by peptide-biphenyl hybrids. We have found that some peptide-biphenyl hybrids, with aromatic amino acids in the peptide chains, inhibit calpain with IC50 values in the nanomolar range. Since the peptide-biphenyl hybrids reported in the present paper do not posses a reactive electrophilic functionality, we hypothesize that they interfere with the activation of calpain by Ca2+, and present experimental and computational results on the binding of peptide-biphenyl hybrids to Ca2+.

Dynamic atropselective resolutions of the peptide-biphenyl hybrids 3-5 were achieved by crystallization from methanol solution. These compounds were studied by single-crystal X-ray diffraction. These hybrids crystallize in highly ordered structures kept by an extensive array of intramolecular and intermolecular hydrogen bonds. The solid-state molecular structure is highly dependent on the substituents on the α-carbon of the amino acid. The presence of additional aromatic rings in the side chain causes the molecules in the crystal to interact through a variety of interactions involving the aromatic rings. The resulting supramolecular structures are helices whose orientation depends on the senses of the chirality of the α-carbon of the amino acid residues and the aryl-aryl bond. © The Royal Society of Chemistry 2004.

We have developed a convenient route for the synthesis of an unsaturated branched sugar bearing a carboxylic acid and an amino group (masked as an azide group) by employing a totally stereoselective Claisen-Johnson rearrangement as the key step. Several Met- and Leu-enkephalin analogues with different substitution patterns at the N- and C-termini were prepared by incorporating this sugar amino acid (SAA) as a substitute for the central Gly-Gly fragment of the parent pentapeptides. © Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

With the objective to understand structural features responsible for the biological activity, novel nonelectrophilic biphenyl derivatives and peptide-biphenyl hybrids have been synthesized and evaluated as calpain I inhibitors. The preliminary results indicate that the presence of additional aromatic rings (besides the biphenyl system) makes these compounds potent calpain inhibitors with IC50 values in the nanomolar range. © 2004 Elsevier Ltd. All rights reserved.

The syntheses of the γ-amino-α,β-unsaturated esters [(R)-4, (S)-5, and (±)-6] are reported. The methodology for the preparation of these triannular heterocycles involves two synthetic sequences from N-substituted amino alcohols: a 'one-pot' sequential Swern oxidation-Wittig reaction and an intramolecular Heck reaction. The γ-amino-α,β-unsaturated ester [(R)-4] has been used for the synthesis of the peptide-heterocycle hybrids (19-21).