19 research outputs found
Organocatalytic vinylogous Mannich reaction of trimethylsiloxyfuran with isatin-derived benzhydryl-ketimines
No full textA family of chiral quaternary 3-aminooxindole butenolides has been synthesized by BINOL-derived phosphoric acid-catalyzed addition of trimethylsiloxyfuran to isatin-derived ketimines. Such a vinylogous Mannich-type reaction was found to produce diastereoisomeric butenolides in good yields and in most cases high enantiomeric excesses. The configurational assignment of the obtained products was safely performed by chemical correlation. A computational study of the transition state allowed rationalizing the obtained stereochemical outcome, highlighting the possible binding modes of the catalyst-imine-nucleophile transition complex
Biocatalysed olefin reduction of 3-alkylidene oxindoles by baker's yeast
No full text3-Substituted oxindoles are very interesting molecules both for their potential biological activity and for their role as starting materials toward more complex oxindole-based structures. These molecules can be prepared by the reduction of a 3-ylidene oxindole precursor by classical metal-catalysed chemical reductions of the olefin. In this work we present a biocatalytic approach for the reduction of oxindole-based olefins using baker's yeast. All the substrates were efficiently reduced in high yields. When an α,Î2-unsaturated ketone was used, the corresponding saturated alcohol was obtained in high yield and ee. To further investigate the enzyme-substrate interactions a molecular docking study was also performed
Multicomponent Approach to Bioactive Peptide-Ecdysteroid Conjugates: Creating Diversity at C6 by Means of the Ugi Reaction
No full textAn efficient multicomponent protocol has been developed to access two different kinds of peptide–ecdysteroid conjugates. The approach exploits the reactivity of the 6-keto-7-ene group of 20-OH-ecdysone, allowing the unprecedented preparation of 6-amino and 6-isocyanide derivatives. The ecdysteroid derivatives were further employed in the Ugi reaction, together with formaldehyde and various structurally diverse carboxylic acids, isocyanides and amines, to afford a small family of potential multidrug-resistance modulators
Organocatalytic Asymmetric Biginelli-like Reaction Involving Isatin
No full textThe first asymmetric, Brønsted acid catalyzed Biginelli-like reaction of a ketone has been developed, employing N-substituted isatins as carbonyl substrates, and urea and alkyl acetoacetates as further components. BINOL-derived phosphoric acid catalysts have been used to achieve the synthesis of a small library of chiral, enantioenriched spiro(indoline-pyrimidine)-diones derivatives. The absolute configuration of the new spiro stereocenter was assessed on diastereoisomeric derivatives through computer-assisted NMR spectroscopy. X-ray diffractometry allowed the disclosure of the overall molecular conformation in the solid state and the characterization of the crystal packing of a Br-substituted Biginelli-like derivative, while computational studies on the reaction transition state allowed us to rationalize the stereochemical outcome
The Carnal Specter: The Virtual Reality User Against Fragmentation
No full textSince Virtual Reality (VR) is characterised by the absence of the frame, the VR user has the impression of being immersed into the image, thus overcoming the distinction between spectacle and spectator. Therefore, the user becomes herself part of the work of art, exposing the limits of the Cartesian dualisms dominating the Western thought and raising critical questions about traditional aesthetic categories. Hence, my paper aims at pondering on the ontological status of the VR user. In opposition to Simon Penny’s argument, which proposes that VR fragments the viewer into a physical body versus a virtual one, my research goal is to clarify that the participant’s physical body and virtual body are inseparable and firmly intertwined. In order to do so, I analyse the VR documentary Send me Home (Evanisko, 2019). The point of departure is the acknowledgment that the VR user is invisible both to herself and to the other characters with whom she shares the virtual space. Following Jacques Derrida’s Specters of Marx, I argue that this invisibility reveals the ontological status of the VR participant as a specter. However, my goal is to show that the spectrality of the user is not in contradiction with her carnality: on the contrary, even when one tries to bracket the body, the body remains vigilant, interpreting the world through its flesh. To conclude, then, I argue that the body is the condition of possibility for the user to feel immersed into the virtual world, and that, contrary to the fragmentation argument, physical body and virtual body cannot be thought as separate.Since Virtual Reality (VR) is characterised by the absence of the frame, the VR user has the impression of being immersed into the image, thus overcoming the distinction between spectacle and spectator. Therefore, the user becomes herself part of the work of art, exposing the limits of the Cartesian dualisms dominating the Western thought and raising critical questions about traditional aesthetic categories. Hence, my paper aims at pondering on the ontological status of the VR user. In opposition to Simon Penny’s argument, which proposes that VR fragments the viewer into a physical body versus a virtual one, my research goal is to clarify that the participant’s physical body and virtual body are inseparable and firmly intertwined. In order to do so, I analyse the VR documentary Send me Home (Evanisko, 2019). The point of departure is the acknowledgment that the VR user is invisible both to herself and to the other characters with whom she shares the virtual space. Following Jacques Derrida’s Specters of Marx, I argue that this invisibility reveals the ontological status of the VR participant as a specter. However, my goal is to show that the spectrality of the user is not in contradiction with her carnality: on the contrary, even when one tries to bracket the body, the body remains vigilant, interpreting the world through its flesh. To conclude, then, I argue that the body is the condition of possibility for the user to feel immersed into the virtual world, and that, contrary to the fragmentation argument, physical body and virtual body cannot be thought as separate
Organocatalytic Access to Enantioenriched Spirooxindole-Based 4-Methyleneazetidines
No full textThis work describes the synthesis of enantioenriched spiro compounds, incorporating the azetidine and the oxindole motifs. The preparation relies on a formal [2 + 2] annulation reaction of isatin-derived N-tert-butylsulfonyl ketimines with allenoates. The asymmetric induction is secured by an organocatalytic strategy, exploiting a bifunctional cinchona-type β-isocupridine-based catalyst. Some post-transformation products, including unexpected spiropyrroline and 3,3-disubstituted oxindole derivatives, are also presented
One step access to oxindole-based β-lactams through Ugi four-center three-component reaction
No full textA multicomponent Ugi reaction involving isatin, isocyanide and β-amino acid components has been developed. The reactions proceeded smoothly to give β-lactam-containing 3,3-disubstituted oxindoles in only one step and generally high yields. When chiral, non racemic, β-amino acids were used, products were obtained as enantiomerically pure β-lactams diastereoisomers, whose relative stereochemistry was determined by X-ray analysis. For one compound, a weak antibacterial activity has been preliminarily highlighted
Phytosterol and γ-Oryzanol Conjugates: Synthesis and Evaluation of their Antioxidant, Antiproliferative, and Anticholesterol Activities
No full textFifteen new multifunctional conjugates were designed and synthesized by chemically linking the steroidal framework of natural occurring γ-oryzanol and γ-oryzanol-derived phytosterols to a wide range of bioactive natural compounds (fatty acids, phenolic acids, amino acids, lipoic acid, retinoic acid, curcumin, and resveratrol). Starting from γ-oryzanol, which is the main component of rice bran oil, this study was aimed at assessing if the conjugation strategy might enhance some γ-oryzanol bioactivities. The antioxidant activity was evaluated through three different mechanisms, namely, DPPH-scavenging activity, metal-chelating activity, and β-carotene-bleaching inhibition. Measurement of the in vitro cell growth inhibitory effects on three different human cancer cellular lines was also carried out, and the potential hypocholesterolemic effect was studied. Compounds 10 and 15 displayed an improved antioxidant activity, with respect to that of γ-oryzanol. Compounds 2, 6, and 12 exerted an antiproliferative activity in the low micromolar range against HeLa and DAOY cells (GI50 < 10 μM). As for the claimed hypocholesterolemic effect of γ-oryzanol, none of the synthesized compounds inhibited the 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a key enzyme in cholesterol biosynthesis
Face-to-Face, or Face-to-Visor. Is Cinematic Virtual Reality the “Ultimate Empathy Machine”?
No full textMy paper makes a comparison between one possible definition of empathy and the spectator’s experience in VR with the aim of assessing whether these two structures are compatible in a more rigorous way. Following the phenomenological works of Maurice Merleau-Ponty and Vittorio Gallese’s writings on embodied simulation, I will define empathy in the VR context as the result of four different conditions: 1) the VR user and the VR character must share the same ontological structure, for the other is a “second self”, therefore 2) the character must be directly accessible in an intersubjective and reversible relation. Furthermore, 3) it is necessary for the VR user to understand the object of the character’s emotion to strengthen the empathetic response provided by the embodied simulation, but 4) this does not ever mean that empathy leads to a total correspondence of state of minds, as the character’s suffering is always different from what the spectator feels while seeing that suffering. Taking these four conditions in mind, I then apply them to the analysis of the VR documentary Clouds over Sidra (Milk, Arora, 2017), which follows the story of Sidra, a refugee child displaced in the Za’atari refugee camp. My conclusion is that VR engenders an occasion of emotional contagion, which is the quite literal infection of the character’s feeling to the VR user.
Keywords: Embodied Simulation, Emotional Contagion, Intersubjective Relation, Phenomenology, Virtual RealityMy paper makes a comparison between one possible definition of empathy and the spectator’s experience in VR with the aim of assessing whether these two structures are compatible in a more rigorous way. Following the phenomenological works of Maurice Merleau-Ponty and Vittorio Gallese’s writings on embodied simulation, I will define empathy in the VR context as the result of four different conditions: 1) the VR user and the VR character must share the same ontological structure, for the other is a “second self”, therefore 2) the character must be directly accessible in an intersubjective and reversible relation. Furthermore, 3) it is necessary for the VR user to understand the object of the character’s emotion to strengthen the empathetic response provided by the embodied simulation, but 4) this does not ever mean that empathy leads to a total correspondence of state of minds, as the character’s suffering is always different from what the spectator feels while seeing that suffering. Taking these four conditions in mind, I then apply them to the analysis of the VR documentary Clouds over Sidra (Milk, Arora, 2017), which follows the story of Sidra, a refugee child displaced in the Za’atari refugee camp. My conclusion is that VR engenders an occasion of emotional contagion, which is the quite literal infection of the character’s feeling to the VR user.
Keywords: Embodied Simulation, Emotional Contagion, Intersubjective Relation, Phenomenology, Virtual Realit
Multicomponent Synthesis and Biological Evaluation of a Piperazine-Based Dopamine Receptor Ligand Library
No full textA series of 1,4-disubstituted piperazine-based
compounds were designed, synthesized, and evaluated as dopamine D2/D3
receptor ligands. The synthesis relies on the key multicomponent split-Ugi
reaction, assessing its great potential in generating chemical diversity
around the piperazine core. With the aim of evaluating the effect
of such diversity on the dopamine receptor affinity, a small library
of compounds was prepared, applying post-Ugi transformations. Ligand
stimulated binding assays indicated that some compounds show a significant
affinity, with <i>K</i><sub>i</sub> values up to 53 nM for
the D2 receptor. Molecular docking studies with the D2 and D3 receptor
homology models were also performed on selected compounds. They highlighted
key interactions at the indole head and at the piperazine moiety,
which resulted in good agreement with the known pharmacophore models,
thus helping to explain the observed structure–activity relationship
data. Molecular insights from this study could enable a rational improvement
of the split-Ugi primary scaffold, toward more selective ligands
