Design Knowledge for Virtual Learning Companions from a Value-centered Perspective

The increasing popularity of conversational agents such as ChatGPT has sparked interest in their potential use in educational contexts but undermines the role of companionship in learning with these tools. Our study targets the design of virtual learning companions (VLCs), focusing on bonding relationships for collaborative learning while facilitating students’ time management and motivation. We draw upon design science research (DSR) to derive prescriptive design knowledge for VLCs as the core of our contribution. Through three DSR cycles, we conducted interviews with working students and experts, held interdisciplinary workshops with the target group, designed and evaluated two conceptual prototypes, and fully coded a VLC instantiation, which we tested with students in class. Our approach has yielded 9 design principles, 28 meta-requirements, and 33 design features centered around the value-in-interaction. These encompass Human-likeness and Dialogue Management, Proactive and Reactive Behavior, and Relationship Building on the Relationship Layer (DP1,3,4), Adaptation (DP2) on the Matching Layer, as well as Provision of Supportive Content, Fostering Learning Competencies, Motivational Environment, and Ethical Responsibility (DP5-8) on the Service Layer

Stereoselective synthesis of cyclobutanes by contraction of pyrrolidines

Here we report a contractive synthesis of multisubstituted cyclobutanes containing multiple stereocenters from readily accessible pyrrolidines using iodonitrene chemistry. Mediated by a nitrogen extrusion process, the stereospecific synthesis of cyclobutanes involves a radical pathway. Unprecedented unsymmetrical spirocyclobutanes were prepared successfully, and a concise, formal synthesis of the cytotoxic natural product piperarborenine B is reported

Cascade aza-Wittig/6π-electrocyclization in the synthesis of 1,6-dihydropyridines

A metal-free protocol for the synthesis of substituted 1,6-dihydropyridines with quaternary stereogenic centers via a cascade aza-Wittig/6π-electrocyclization process has been developed. The high functional group compatibility and broad scope of this method were demonstrated by using a wide range of easily available vinyliminophosphoranes and ketones, with yields up to 97%. A modification of the obtained products allowed for an increase in complexity and chemical diversity. Finally, attempts for asymmetric synthesis of 1,6-dihydropyridines are demonstrated

Synthesis and reactivity of silylated tetrathiafulvalenes

Novel organosilylated tetrathiafulvalenes (TTFs) possessing Si–H or Si–Si bonds have been synthesised. The crystal structures of several derivatives have been determined by X-ray diffraction, including that of dimeric (Si2Me4)(TTF)2 (11) incorporating a diatomic SiMe2–SiMe2 linker. Cyclic voltammetry measurements in all cases show two oxidation waves. DFT calculations were performed to rationalize the absence of an electronic communication between the two TTF moieties of 11 through the disilanyl spacer. The reactivity of the Si–H bond has been exploited to prepare the dinuclear complex [{Ru(CO)4}2{μ-(Me2Si)4TTF}] (14), starting from Ru3(CO)12 and TTF(SiMe2H)4 (1). Treatment of 14 with 2 equiv. of PPh3 or dppm results in selective substitution of a CO ligand trans to a SiMe2 group to afford mer-[{Ru(PPh3)(CO)3}2{μ-(Me2Si)4TTF}] (13) and mer-[{Ru(CO)3}2(η1-dppm){μ-(Me2Si)4TTF}] (16). Attempts to transform the Si–H bonds of some TTF(SiMe2H)n (n = 1, 2) into Si–O functions using stoichiometric amounts of water in the presence of tris(dibenzylideneacetone)dipalladium(0) were unsuccessful. Quantitative cleavage of the CTTF–Si bond was observed instead of formation of TTF-based-siloxanes. Essays of catalytic bis-silylation of phenylacetylene with 11 and TTF(SiMe2-SiMe3) (9) in the presence of Pd(OAc)2/1,1,3,3-tetramethylbutylisocyanide failed. Again, cleavage of the CTTF–Si bond was noticed

Identification of a Novel Pseudo-Natural Product Type IV IDO1 Inhibitor Chemotype

Natural product (NP)-inspired design principles provide invaluable guidance for bioactive compound discovery. Pseudo-natural products (PNPs) are de novo combinations of NP fragments to target biologically relevant chemical space not covered by NPs. We describe the design and synthesis of apoxidoles, a novel pseudo-NP class, whereby indole- and tetrahydropyridine fragments are linked in monopodal connectivity not found in nature. Apoxidoles are efficiently accessible by an enantioselective [4+2] annulation reaction. Biological evaluation revealed that apoxidoles define a new potent type IV inhibitor chemotype of indoleamine 2,3-dioxygenase 1 (IDO1), a heme-containing enzyme considered a target for the treatment of neurodegeneration, autoimmunity and cancer. Apoxidoles target apo-IDO1, prevent heme binding and induce unique amino acid positioning as revealed by crystal structure analysis. Novel type IV apo-IDO1 inhibitors are in high demand, and apoxidoles may provide new opportunities for chemical biology and medicinal chemistry research

Enantioselective synthesis of five-membered-ring atropisomers with a chiral Rh(III) complex

Axially chiral atropisomeric compounds are widely applied in asymmetric catalysis and medicinal chemistry, and efficient methods for their synthesis are in high demand. This applies in particular to atropisomers derived from five-membered aromatic rings because their lower barrier for rotation among the biaryl axis limits their asymmetric synthesis. We report here an enantioselective C–H functionalization method using our chiral RhJasCp complex for the synthesis of the biaryl atropisomer types that can be accessed from three different five-membered-ring heterocycles

Dynamic catalytic highly enantioselective 1,3‐dipolar cycloadditions

In dynamic covalent chemistry, reactions follow a thermodynamically controlled pathway through equilibria. Reversible covalent-bond formation and breaking in a dynamic process enables the interconversion of products formed under kinetic control to thermodynamically more stable isomers. Notably, enantioselective catalysis of dynamic transformations has not been reported and applied in complex molecule synthesis. We describe the discovery of dynamic covalent enantioselective metal-complex-catalyzed 1,3-dipolar cycloaddition reactions. We have developed a stereodivergent tandem synthesis of structurally and stereochemically complex molecules that generates eight stereocenters with high diastereo- and enantioselectivity through asymmetric reversible bond formation in a dynamic process in two consecutive Ag-catalyzed 1,3-dipolar cycloadditions of azomethine ylides with electron-poor olefins. Time-dependent reversible dynamic covalent-bond formation gives enantiodivergent and diastereodivergent access to structurally complex double cycloadducts with high selectivity from a common set of reagents

PERENCANAAN KEBUTUHAN MATERIAL (PKM) PADA PRODUKSI KINCIR ANGIN KAPASITAS 100 WATT

Banda Ace

The pseudo‐natural product rhonin targets RHOGDI

For the discovery of novel chemical matter generally endowed with bioactivity, strategies may be particularly efficient that combine previous insight about biological relevance, e.g., natural product (NP) structure, with methods that enable efficient coverage of chemical space, such as fragment-based design. We describe the de novo combination of different 5-membered NP-derived N-heteroatom fragments to structurally unprecedented “pseudo-natural products” in an efficient complexity-generating and enantioselective one-pot synthesis sequence. The pseudo-NPs inherit characteristic elements of NP structure but occupy areas of chemical space not covered by NP-derived chemotypes, and may have novel biological targets. Investigation of the pseudo-NPs in unbiased phenotypic assays and target identification led to the discovery of the first small-molecule ligand of the RHO GDP-dissociation inhibitor 1 (RHOGDI1), termed Rhonin. Rhonin inhibits the binding of the RHOGDI1 chaperone to GDP-bound RHO GTPases and alters the subcellular localization of RHO GTPases