Numerous efficient synthetic methods for enantioselective indole functionalizations have emerged in recent years. This review summarizes the major achievements in the transition-metal-catalyzed ...enantioselective indole functionalization reactions since 2010 and focuses on C-C bond formation processes, including alkylations, arylations, cycloaddition reactions, and other reactions. It intends to give a compendious overview of the significant progress achieved in this area.
Recent progress on the transition-metal-catalyzed enantioselective functionalization reaction of indoles is reviewed, which is mainly focused on asymmetric indole alkylations, arylations, cycloaddition reactions, and other reactions.
3D bioprinting technology provides programmable and customizable platforms to engineer cell‐laden constructs mimicking human tissues for a wide range of biomedical applications. However, the ...encapsulated cells are often restricted in spreading and proliferation by dense biomaterial networks from gelation of bioinks. Herein, a cell‐benign approach is reported to directly bioprint porous‐structured hydrogel constructs by using an aqueous two‐phase emulsion bioink. The bioink, which contains two immiscible aqueous phases of cell/gelatin methacryloyl (GelMA) mixture and poly(ethylene oxide) (PEO), is photocrosslinked to fabricate predesigned cell‐laden hydrogel constructs by extrusion bioprinting or digital micromirror device‐based stereolithographic bioprinting. The porous structure of the 3D‐bioprinted hydrogel construct is formed by subsequently removing the PEO phase from the photocrosslinked GelMA hydrogel. Three different cell types (human hepatocellular carcinoma cells, human umbilical vein endothelial cells, and NIH/3T3 mouse embryonic fibroblasts) within the 3D‐bioprinted porous hydrogel patterns show enhanced cell viability, spreading, and proliferation compared to the standard (i.e., nonporous) hydrogel constructs. The 3D bioprinting strategy is believed to provide a robust and versatile platform to engineer porous‐structured tissue constructs and their models for a variety of applications in tissue engineering, regenerative medicine, drug development, and personalized therapeutics.
An aqueous two‐phase emulsion bioink is developed to create bioprinted porous‐structured hydrogel constructs. Interconnected micropores within the bioprinted hydrogel constructs enhance the growth, spreading, and proliferation of encapsulated living cells.
Conspectus Olefin functionalization represents one of the most important synthetic transformations in organic synthesis. Over the past decades, palladium-catalyzed enantioselective Heck reactions, ...and Heck/anion-capture domino sequences through olefin carbopalladation followed by termination of the resulting alkyl-Pd species have been extensively developed. Extension of the coupling partners from classical olefins to other π-components would enable further advances and open new space in this field. Aromatics are important and easily available bulk chemicals. Dearomative transformation of endocyclic aromatic π-bonds via the Heck reaction pathway provides an efficient and straightforward route to structurally diverse alicyclic compounds. Nevertheless, major challenges for this transformation include aromaticity breaking and reactivity and selectivity issues. Recently, we have engaged in developing catalytic enantioselective dearomative Heck reactions and related domino reactions. A range of heteroarenes and naphthalenes have been employed as novel π-coupling partners in these reactions. Through dearomative migratory insertion of endocyclic aromatic C–C π-bonds followed by interception of the transient alkyl-Pd species, enantioselective Heck reactions, reductive Heck reactions, Heck/anion-capture difunctionalization reactions, and heteroarenyne cycloisomerization reactions have been established. Relying on β-H elimination of the alkyl-Pd intermediate, we realized enantioselective dearomative Heck reactions with a range of aromatic partners, including heterocyclic indoles, pyrroles, furans, benzofurans, and more challenging carbocyclic naphthalenes. In order to avoid the utilization of organohalide electrophiles, heteroarenyne cycloisomerization reaction was developed by merging intermolecular alkyne hydropalladation with intramolecular dearomative Heck reaction. Cycloisomerization of alkyne-tethered indoles delivered chiral indolines in excellent enantioselectivities with 100% atom economy. On the other hand, Heck/anion-capture domino sequences were established through nucleophilic trapping of the alkyl-Pd intermediate. When HCO2Na was employed as a capturing reagent, the enantioselective dearomative reductive Heck reaction of indoles was realized. By employing other nucleophiles, including alkynes, N-sulfonylhydrazones, and organoboron reagents, we developed a series of dearomative difunctionalization reactions. Two vicinal stereocenters with excellent enantio- and diastereoselectivities were constructed in the corresponding Heck/Sonogashira, Heck/vinylation, and Heck/borylation reactions. Moreover, dearomative 1,4-diarylation of naphthalenes was developed through Heck/Suzuki domino reactions, in which competitive C–H arylation and the direct Suzuki reaction were almost fully inhibited in the presence of a spiro-phosphoramidite ligand. In this Account, we provide a panoramic view of our results since 2015 on enantioselective Heck reactions and related domino sequences by extending the coupling partners from classical olefins to aromatic systems. Investigations outlined in this Account established straightforward and efficient access to a variety of structurally diverse chiral heteropolycyclic molecules starting from simple and planar aromatic compounds.
Palladium‐catalyzed enantioselective dearomative arylalkynylation of N‐substituted indoles, through a Heck/Sonogashira sequence, was established using a new BINOL‐based phosphoramidite as the chiral ...ligand. A wide range of 2,3‐disubstituted indolines, bearing vicinal quaternary and tertiary stereocenters, were efficiently constructed in one step with excellent enantioselectivities (up to 97 % ee) and diastereoselectivities (>20:1).
Double the function: A highly enantioselective dearomative arylalkynylation of N‐substituted indoles with alkynes has been established by using palladium and a BINOL‐based phosphoramidite as the chiral ligand. A wide range of 2,3‐disubstituted indolines, bearing vicinal tertiary and quaternary stereocenters, were constructed in one step with excellent enantio‐ and diastereoselectivities.
Current modeling of infectious diseases allows for the study of complex and realistic scenarios that go from the population to the individual level of description. However, most epidemic models ...assume that the spreading process takes place on a single level (be it a single population, a metapopulation system, or a network of contacts). In particular, interdependent contagion phenomena can be addressed only if we go beyond the scheme-one pathogen-one network. In this paper, we propose a framework that allows us to describe the spreading dynamics of two concurrent diseases. Specifically, we characterize analytically the epidemic thresholds of the two diseases for different scenarios and compute the temporal evolution characterizing the unfolding dynamics. Results show that there are regions of the parameter space in which the onset of a disease’s outbreak is conditioned to the prevalence levels of the other disease. Moreover, we show, for the susceptible-infected-susceptible scheme, that under certain circumstances, finite and not vanishing epidemic thresholds are found even at the limit for scale-free networks. For the susceptible-infected-removed scenario, the phenomenology is richer and additional interdependencies show up. We also find that the secondary thresholds for the susceptible-infected-susceptible and susceptible-infected-removed models are different, which results directly from the interaction between both diseases. Our work thus solves an important problem and paves the way toward a more comprehensive description of the dynamics of interacting diseases.
The extensively developed ene‐type enantioselective cycloisomerization of classical 1,n‐enynes provides an efficient approach to chiral cyclic 1,4‐dienes. In contrast, the catalytic asymmetric ...heteroarenyne (heteroarene–alkyne) cycloisomerization involving the dearomative transformation of endocyclic aromatic C=C bonds remains unknown. Herein, we communicate a PdH‐catalyzed enantioselective heteroarenyne cycloisomerization reaction of alkyne‐tethered indole substrates (formal 1,5‐ and 1,6‐enynes). Based on this strategy, a variety of structurally diverse chiral spiro and fused indoline derivatives bearing quaternary stereocenters and exocyclic C=C bonds are afforded in moderate to excellent yields and excellent enantioselectivities (up to 98 % ee). The classical ene‐type enantioselective 1,5‐enyne cycloisomerization of N‐vinylpropiolamides is also developed to afford chiral 2‐pyrrolones in good to excellent ee values.
A palladium‐catalyzed enantioselective ene‐type cycloisomerization of heteroarenynes has been developed with alkyne‐tethered indoles as substrates. The reaction provides an efficient avenue for the synthesis of structurally diverse indolines bearing quaternary stereocenters in moderate to excellent yields and excellent enantioselectivities (up to 98 % ee).
In the research realm of game theory, interdependent networks have extended the content of spatial reciprocity, which needs the suitable coupling between networks. However, thus far, the vast ...majority of existing works just assume that the coupling strength between networks is symmetric. This hypothesis, to some extent, seems inconsistent with the ubiquitous observation of heterogeneity. Here, we study how the heterogeneous coupling strength, which characterizes the interdependency of utility between corresponding players of both networks, affects the evolution of cooperation in the prisoner's dilemma game with two types of coupling schemes (symmetric and asymmetric ones). Compared with the traditional case, we show that heterogeneous coupling greatly promotes the collective cooperation. The symmetric scheme seems much better than the asymmetric case. Moreover, the role of varying amplitude of coupling strength is also studied on these two interdependent ways. Current findings are helpful for us to understand the evolution of cooperation within many real-world systems, in particular for the interconnected and interrelated systems.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Astrocytes, microglia, and tanycytes play active roles in the regulation of hypothalamic feeding circuits. These non-neuronal cells are crucial in determining the functional interactions of specific ...neuronal subpopulations involved in the control of metabolism. Recent advances in biology, optics, genetics, and pharmacology have resulted in the emergence of novel and highly sophisticated approaches for studying hypothalamic neuronal-glial networks. Here we summarize the progress in the field and argue that glial-neuronal interactions provide a core hub integrating food-related cues, interoceptive signals, and internal states to adapt a complex set of physiological responses operating on different timescales to finely tune behavior and metabolism according to metabolic status. This expanding knowledge helps to redefine our understanding of the physiology of food intake and energy metabolism.
A palladium-catalyzed dearomative arylborylation of indoles is reported, which provides straightforward access to structurally diverse indolines bearing vicinal tetrasubstituted and borylated ...trisubstituted stereocenters in moderate to good yields with excellent diastereoselectivities. By using a BINOL-based chiral phosphoramidite ligand and an sp 2 –sp 3 mixed-boron reagent, an enantioselective dearomative arylborylation was achieved and chiral boron-containing products were accessed in up to 94% ee. Synthetic tranformations of the resulting organoborons were conducted to afford a number of unique indoline derivatives.
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