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There has been a recent upsurge in research aimed at synthesizing inherently chiral molecules devoid of point, axial, planar and helical chiralities. We present herein our design and enantioselective synthesis of a series of inherently chiral macrocycles. These compounds, termed nor-heteracalixaromatics, feature a biaryl bond that replaces one of the aryl-heteroatom-aryl linkages found in classic heteracalix[4]aromatics. Macrocyclization of linear achiral substrates via an intramolecular Suzuki-Miyaura cross-coupling reaction affords the 15-membered cyclophane without any chiral elements in high yields and enantioselectivities. Notably, the formation of the aryl-aryl bond does not induce axial chirality at the biaryl linkage. Instead, it restricts the free rotation of an aromatic ring located four bonds away, leading to the inherent chirality of the macrocycle. The intriguing chiroptical properties of these compounds made them promising platform for the development of CPL emitters.
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Pulmonary hypertension (PH) is a progressive fatal disease with no cure. Canagliflozin (CANA), a novel medication for diabetes, has been found to have remarkable cardiovascular benefits. However, few studies have addressed the effect and pharmacological mechanism of CANA in the treatment of PH. Therefore, our study aimed to investigate the effect and pharmacological mechanism of CANA in treating PH. First, CANA suppressed increased pulmonary artery pressure, right ventricular hypertrophy, and vascular remodeling in both mouse and rat PH models. Network pharmacology, transcriptomics, and biological results suggested that CANA could ameliorate PH by suppressing excessive oxidative stress and pulmonary artery smooth muscle cell proliferation partially through the activation of PPARγ. Further studies demonstrated that CANA inhibited phosphorylation of PPARγ at Ser225 (a novel serine phosphorylation site in PPARγ), thereby promoting the nuclear translocation of PPARγ and increasing its ability to resist oxidative stress and proliferation. Taken together, our study not only highlighted the potential pharmacological effect of CANA on PH but also revealed that CANA-induced inhibition of PPARγ Ser225 phosphorylation increases its capacity to counteract oxidative stress and inhibits proliferation. These findings may stimulate further research and encourage future clinical trials exploring the therapeutic potential of CANA in PH treatment.
Assuntos
Canagliflozina , Proliferação de Células , Hipertensão Pulmonar , Estresse Oxidativo , PPAR gama , Animais , Masculino , Camundongos , Ratos , Canagliflozina/farmacologia , Canagliflozina/uso terapêutico , Proliferação de Células/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/metabolismo , Camundongos Endogâmicos C57BL , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , PPAR gama/metabolismo , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/metabolismo , Ratos Sprague-Dawley , Remodelação Vascular/efeitos dos fármacos , Serina/química , Serina/metabolismoRESUMO
Caricature generation aims to translate portrait photos into caricatures with exaggerated and hand-drawn artistic styles. Previous methods faced challenges in creating diverse and meaningful exaggeration effects, yielding unsatisfactory and uncontrollable results. To overcome this, we proposed ETCari, a novel weakly supervised exaggeration transfer network. ETCari enables the learning of diverse exaggeration caricature styles from various artists, better meeting individual customization requirements and achieving diversified exaggeration while retaining identity features. Specifically, we use the TPS control point deformation field as the ground truth, serving as the loss for weakly supervised learning to address the challenge of no labels. We convert input to an intermediate modality for domain adaptation, training a teacher model. Subsequently, we perform cross-modal knowledge distillation to train the student model, simplifying preprocessing during inference and avoiding the impact of face parser errors. Experiments on the WebCaricature dataset demonstrate that ETCari effectively performs exaggeration transfer, generating appealing caricatures.
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We report herein the synthesis of highly enantiopure inherently chiral N3,O-calix[2]arene[2]triazines from enantioselective macrocyclization enabled by chiral phosphoric acid-catalyzed intramolecular nucleophilic aromatic substitution reaction. In contrast to documented examples, the inherent chirality of the acquired compounds arises from one heteroatom difference in the linking positions of heteracalix[4](het)arenes.
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In contrast to a plethora of macrocyclic and cage compounds, spirophanes have remained largely unexplored. We report herein the construction, structure and properties of unprecedented tetrahomo corona[4]arene-based ditopic and tritopic macrocycles of spiro structures. Synthesis was conveniently achieved by means of an efficient SNAr reaction from simple and commercially available starting materials. Racemic samples were resolved into enantiopure chiral tetrahomo i-corona[4]arenes, spirophanes and bispirophanes which show interesting chiroptical properties. The acquired electron-deficient macrocyclic compounds were found to adopt unique conformational structures and to form distinct complexes with TTF in the solid state. Our study provides a new opportunity to develop multitopic macrocycles of different topologies which have potential applications in supramolecular chemistry.
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The fungal taxa belonging to the Clavicipitaceae (Hypocreales, Ascomycota) are widely distributed and include diverse saprophytic, symbiotic and pathogenic species that are associated with soils, insects, plants, fungi and invertebrates. In this study, we identified two new fungal taxa belonging to the family Clavicipitaceae that were isolated from soils collected in China. Morphological characterisation and phylogenetic analyses showed that the two species belong to Pochonia (Pochoniasinensissp. nov.) and a new genus for which we propose Paraneoaraneomycesgen. nov. in Clavicipitaceae.
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Despite their interesting stereochemistry and potential applications in (supramolecular) chemistry and chiroptical materials, inherently chiral macrocyclic compounds remain rare and are largely unexplored. We report herein a fragment coupling method to construct ABAC- and ABCD-type inherently chiral heteracalix[4]aromatics. The synthesis involves SNAr CuI-catalyzed Ullmann coupling and aliphatic nucleophilic substitution reactions as key steps using readily available starting materials. Postmacrocyclization functionalization reactions enabled the production of amino-substituted and (benzo[d])imidazole-2-(thi)one-bearing heteracalix[4]aromatics. Enantiopure ABCD-type macrocycles were obtained from resolution.
Assuntos
Compostos Macrocíclicos , Estrutura Molecular , Estereoisomerismo , Calixarenos/químicaRESUMO
The purpose of this study was to investigate the neural activity evoked by facial attractiveness in conscious and subliminal conditions. The 41 participants judged facial attractiveness in a conscious condition and a subliminal condition (backward masking paradigm). The event-related potential (ERP) analysis indicated that in the conscious condition, more attractive faces elicited a longer N1 (80-120 ms) latency than less attractive faces. Moreover, more attractive female faces elicited a larger late positive component (LPC) (350-550 ms) amplitude than less attractive female faces. In the subliminal condition, more attractive faces elicited a longer P1 (140-180 ms) latency than less attractive faces. The present study demonstrated that more attractive faces evoked different early-stage ERPs from that evoked by less attractive faces in both conscious and subliminal conditions. However, the processing of facial attractiveness is obviously weakened in the subliminal condition.
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Asymmetric synthesis of enantioenriched zigzag-type molecular belts featuring copper/H8-binaphthol-catalyzed kinetic resolution of a resorcinarene derivative and subsequent transformations was developed. The acquired rigid and C4-symmetric belt exhibited remarkably enhanced photophysical and chiroptical properties in comparison to its conformationally fluxional macrocyclic precursor.
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Hydrocarbon belts have drawn great attention because of their unique structures and tantalizing properties. Although a few belts and heteroatom-doped analogs have been synthesized, belt molecules containing non-hexagonal rings remain rare. Herein we report the construction and application of unprecedented zigzag-type hydrocarbon belts which contain functionalized eight-membered rings. The synthesis features fourfold intramolecular acylation reactions of resorcin[4]arene-derived intermediates, which affords C4 -symmetric tetrabenzobelt[4]arene[4]cyclooctatrienones. Stereoselective ketone reduction with LiAlH4 and nucleophilic addition with alkynyllithiums provide the corresponding tetrahydroxylated belts. The tetraol and its methyl ether are powerful and selective hosts to form 2 : 1 and 1 : 1 complexes with cesium ion, respectively, with binding constants up to (1.71±0.33)×1011 â M-2 and (1.50±0.16)×106 â M-1 . In addition, enantiopure C4 -symmetric belts can emit CPL with |glum | being around 0.01.
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Under the catalysis of PdBr2 and a chiral phosphoramidite ligand, the upper-rim mono (2-bromoaroyl)-substituted calix[4]arene derivatives underwent a facile enantioselective desymmetrization reaction to afford 9H-fluorene-embedded inherently chiral calixarenes in good yields with excellent enantioselectivities. The transannular dehydrogenative arene-arene coupling reaction proceeded most probably through an oxidative addition of the Caryl-Br bond to a ligated palladium catalyst followed by a sequence of an enantioselective 1,5-palladium migration and an intramolecular C-H arylation sequence. This new family of inherently chiral calixarenes possesses unique chiroptical properties thanks to their highly rigid structure induced by the 9H-fluorene segment.
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Two new species, Acremoniumcapsici and A.guizhouense, isolated from the rhizosphere soil of Capsicumannuum, are described and illustrated. Two-locus DNA sequences based on phylogeny, in combination with the morphology of the asexual morph, were used to characterize these species. In the phylogenetic tree, both new species clustered into a monophyletic clade with strong support, distinct from other previously known species of Acremonium. The new species differed from their allied species in their morphology.
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Herein we report a two-directional cyclization strategy for the synthesis of highly strained depth-expanded oxygen-doped chiral molecular belts of the zigzag-type. From the easily accessible resorcin[4]arenes, an unprecedented cyclization cascade generating fused 2,3-dihydro-1H-phenalenes has been developed to access expanded molecular belts. Stitching up the fjords through intramolecular nucleophilic aromatic substitution and ring-closing olefin metathesis reactions furnished a highly strained O-doped C2 -symmetric belt. The enantiomers of the acquired compounds exhibited excellent chiroptical properties. The calculated parallelly aligned electric (µ) and magnetic (m) transition dipole moments are translated to the high dissymmetry factor (|glum | up to 0.022). This study provides not only an appealing and useful strategy for the synthesis of strained molecular belts but also a new paradigm for the fabrication of belt-derived chiroptical materials with high CPL activities.
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A diversity of unprecedented chiral aza-crown ethers were synthesized straightforwardly from readily available and inexpensive aza-crown ethers. Catalyzed by a chiral phosphoric acid, desymmetrization of an array of symmetric N-arylated aza-crown ethers through tert-amino reaction proceeded efficiently under mild conditions to produce novel tetrahydroquinoline-fused aza-crown ethers in good to excellent yields with up to 96% ee. Our strategy opens a new route to functionalized chiral crown ethers.
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The small Stokes shift and weak emission in the solid state are two main shortcomings associated with the boron-dipyrromethene (BODIPY) family of dyes. This study presents the design, synthesis and luminescent properties of boron difluoro complexes of 2-aryl-5-alkylamino-4-alkylaminocarbonylthiazoles. These dyes display Stokes shifts (Δλ, 77-101â nm) with quantum yields (ÏFL ) up to 64.9 and 34.7 % in toluene solution and in solid state, respectively. Some of these compounds exhibit dual fluorescence and room-temperature phosphorescence (RTP) emission properties with modulable phosphorescence quantum yields (ÏPL ) and lifetime (τp up to 251â µs). The presence of intramolecular H-bonds and negligible π-π stacking revealed by X-ray crystal structure might account for the observed large Stokes shift and significant solid-state emission of these fluorophores, while the enhanced spin-orbit coupling (SOC) of iodine and the self-assembly driven by halogen bonding, π-π and C-H π interactions could be responsible for the observed RTP of iodine containing phosphors.
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Recent decades have witnessed a resurgence of the study of copper-catalyzed organic reactions. As the surrogate of noble metal catalysts, copper salts have been shown to exhibit remarkable versatility in activating various C-H bonds enabling the construction of diverse carbon-carbon and carbon-heteroatom bonds. Advantageously, copper salts are also naturally abundant, inexpensive, and less toxic in comparison to precious metals. Despite significant developments in synthesis, the mechanism of copper catalysis remains elusive. Hypothetical pathways such as the two-electron Cu(III)/Cu(I) and Cu(II)/Cu(0) catalytic cycles and the one-electron Cu(II)/Cu(I) catalytic cycle have been invoked to diagram C-H bond transformations because of the formidable challenges to isolate and characterize transient high valent organocopper intermediates. In fact, organocopper chemistry has been dominated for a long time by the acknowledged nucleophilic organocopper(I) compounds. Since the beginning of the new millennium, we have been systematically studying the supramolecular chemistry of heteracalix[n]aromatics. Owing to the ease of their synthesis and selective functionalizations, self-tunable conformation and cavity structures resulting from the interplay of heteroatoms with aromatic subunits, and outstanding properties in molecular recognition and self-assembly, heteracalix[n]aromatics have become a class of privileged synthetic macrocyclic hosts. Our journey to the chemistry of high valent organocopper compounds started with a serendipitous discovery of the facile formation of a stable organocopper compound, which contains astonishingly a Ph-Cu(III) σ-bond under very mild aerobic conditions. When we examined routinely the effect of the macrocyclic structures on noncovalent complexation properties, titration of tetraazacalix[1]arene[3]pyridine with Cu(ClO4)2·6H2O resulted in the precipitation of dark-purple crystals of phenylcopper(III) diperchlorate. Our curiosity about the transformation of an arene C-H bond into an Ar-Cu(III) bond prompted us to conduct an in-depth investigation of the reaction of macrocyclic arenes with copper(II) salts, leading to the isolation of arylcopper(II) compounds which are unprecedented and the missing link in organocopper chemistry. With structurally well-defined organometallics in hand, we have explored extensively the reactivities of both arylcopper(II) and arylcopper(III) compounds, demonstrating their versatility and uniqueness in chemical synthesis. Novel and fascinating arene C-H transformations under copper catalysis have been developed. Using acquired high valent arylcopper compounds as molecular probes, and employing the functionalizations of tetraazacalix[1]arene[3]pyridines as model reactions, we have revealed the diverse mechanisms of copper-promoted arene C-H bond reactions. Elusive reaction pathways of some copper-catalyzed C-X bond activations have also been unraveled. In the meantime, we have also witnessed pleasingly the rapid development of field with the advent of new high valent organocopper compounds. Without any doubt, studies of the synthesis, reactivity, and catalysis of high valent organocopper compounds have been reshaping the field of organocopper chemistry. This Account summarizes our endeavors to explore the chemistry of structurally well-defined arylcopper(II) and arylcopper(III) compounds and the mechanisms of copper-catalyzed arene C-H and C-X bond transformations. We hope this Account will inspire chemists to study thoroughly the fundamentals and the cutting-edge catalysis of high valent organocopper compounds advancing and redefining the discipline of organocopper chemistry.
Assuntos
Cobre , Compostos de Cobre Orgânico , Carbono , Catálise , Cobre/química , Sondas Moleculares , Piridinas/química , SaisRESUMO
Despite their unique structures, tantalizing properties, and potential applications in carbon nanoscience and technology, the synthesis and functionalization of zigzag hydrocarbon nanobelts have remained largely unexplored until recently. Reported herein is the selective transformations of belt[4]arene[4]tropilidenes and their application in the construction of novel belts. The oxidation of belt[4]arene[4]tropilidene with benzeneseleninic anhydride under controlled conditions selectively afforded mono- to tetrakis(α-diketone)-functionalized belt intermediates. A subsequent condensation reaction with 1,2-phenylenediacetonitrile and 1,2-phenylenediamine produced a diversity of unprecedented belts with various macrocyclic cavities.
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Starting from readily available tetratriflated resorcin[4]arene derivatives, C4-symmetric 1,3,5,7(1,3)-tetrabenzenacyclooctaphane tetraamines were synthesized conveniently by means of Pd-catalyzed C-N bond coupling reaction with diphenylmethanimine followed by hydrolysis. Subsequent Sandmeyer reaction and sulfonylation reaction efficiently afforded the corresponding tetraazide and tetrasulfonamide products, respectively. Upon treatment with PhI(OAc)2, tetrasulfonamides underwent facile oxidative transannular cyclization reaction to produce mono- and dispiro macrocyclic compounds selectively rather than N4-octahydrobelt[8]arenes. Conformational structures of resulting macrocycles are presented, and the reaction mechanism is discussed.
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Despite the aesthetically appealing structures and tantalizing physical and chemical properties, zigzag hydrocarbon belts and their heteroatom-embedded analogues remain challenging synthetic targets. We report herein the synthesis of diverse O/N-doped zigzag hydrocarbon belts based on selective bridging of the fjords of resorcin[4]arene derivatives through intramolecular SN Ar and palladium-catalyzed intermolecular C-N bond formation reactions. Preorganized conformations of mono-macrocyclic, half-belt and quasi-belt compounds were revealed to facilitate cyclization reactions to construct heteroatom-linked octahydrobelt[8]arenes. The acquired products had strained square-prism-shaped belt structures in which all six-membered heterocyclic rings adopted an unusual boat conformation with equatorially configured alkyl groups. The unprecedented heteroatom-bearing belts also exhibited different photophysical and redox properties to those of octahydrobelt[8]arene analogues.
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We report herein an efficient cascade strategy for the rapid construction of a highly enantioenriched erythrinane core skeleton. Under the sequential catalysis of a chiral Cr(III)(salen)Cl and InCl3, cyclohexanone-derived tertiary enamides undergo an intramolecular enantioselective nucleophilic addition followed by diastereoselective Pictet-Spengler cyclization. This method is highly enantio- and diastereoselective, leading to diverse erythrina alkaloid derivatives as the sole diastereoisomer with up to 98% ee.