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Fractional quantum Hall (FQH) states are known for their robust topological order and possess properties that are appealing for applications in fault-tolerant quantum computing. An engineered quantum platform would provide opportunities to operate FQH states without an external magnetic field and enhance local and coherent manipulation of these exotic states. We demonstrate a lattice version of photon FQH states using a programmable on-chip platform based on photon blockade and engineering gauge fields on a two-dimensional circuit quantum electrodynamics system. We observe the effective photon Lorentz force and butterfly spectrum in the artificial gauge field, a prerequisite for FQH states. After adiabatic assembly of Laughlin FQH wave function of 1/2 filling factor from localized photons, we observe strong density correlation and chiral topological flow among the FQH photons. We then verify the unique features of FQH states in response to external fields, including the incompressibility of generating quasiparticles and the smoking-gun signature of fractional quantum Hall conductivity. Our work illustrates a route to the creation and manipulation of novel strongly correlated topological quantum matter composed of photons and opens up possibilities for fault-tolerant quantum information devices.
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BACKGROUND: Inositol polyphosphate 4-phosphatase type II (INPP4B) has been identified as a tumor repressor in several human cancers while its role in endometrial cancer has not been investigated yet. Therefore, the current study was designed to determine whether INPP4B participates in the progression of endometrial cancer by utilizing clinical data and experimental determination. MATERIALS AND METHODS: We first include six chemotherapy-treated patients with recurrent and metastatic endometrioid carcinoma to determine the relationship between INPP4B mutation and relative tumor burden. By using siRNA-mediated gene silencing and vector-mediated gene overexpression, we further determined the effect of manipulating INPP4B expression on the proliferation, invasion, and survival of endometrial cancer cells. Furthermore, the repressing effect of INPP4B together with its role in chemotherapy was further validated by xenograft tumor-bearing mice models. Western blot analysis was used to explore further downstream signaling modulated by INPP4B expression manipulation. RESULTS: Two of the patients were found to have INPP4B mutations and the mutation frequency of INPP4B increased during the progression of chemotherapy resistance. Endometrial cancer cells with silenced INPP4B expression were found to have promoted tumor cell proliferation, invasion, and survival. Endometrial cancer cells overexpressing INPP4B were found to have decreased tumor cell proliferation, invasion, and survival. An in vivo study using six xenograft tumor-bearing mice in each group revealed that INPP4B overexpression could suppress tumor progression and enhance chemosensitivity. Furthermore, INPP4B overexpression was found to modulate the activation of Wnt3a signaling. CONCLUSION: The current study suggested that INPP4B could be a suppressor in endometrial cancer progression and might be a target for endometrial cancer treatment. Also, INPP4B might serve as a predictor of chemosensitivity determination.
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Movimiento Celular , Proliferación Celular , Neoplasias Endometriales , Invasividad Neoplásica , Monoéster Fosfórico Hidrolasas , Humanos , Femenino , Neoplasias Endometriales/patología , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Monoéster Fosfórico Hidrolasas/genética , Monoéster Fosfórico Hidrolasas/metabolismo , Animales , Línea Celular Tumoral , Ratones , Ratones Desnudos , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/metabolismo , Persona de Mediana Edad , Supervivencia Celular , Regulación Neoplásica de la Expresión Génica , MutaciónRESUMEN
A new strategy focusing on the last-stage asymmetric assembly of the ring D, which inherently possesses the densest part of stereogenic centers and functional groups in the A/B/C/D ring system of (-)-cephalotaxine, has been developed, in which a novel Rh-catalyzed asymmetric (2 + 3) annulation of tertiary enamides with enoldiazoacetates is designed and explored for enantioselective construction of the crucial cyclopentane ring D bearing a unique spirocyclic aza-quaternary stereocenter. Based on the expeditious access of chiral functionalized building block with the tetracyclic A/B/C/D ring system, a concise enantioselective total synthesis of (-)-cephalotaxine starting from readily available homopiperonyl alcohol has been achieved in nine steps with only two column chromatography purifications. Following the tactical introduction of the Meinwald rearrangement, enantioselective divergent syntheses of (-)-cephalotine B with an additional C3-O-C11 oxo-bridged bond (14 steps), (-)-fortuneicyclidin B with an unprecedented C3-C10 bond (14 steps), and its 2-epimer (-)-fortuneicyclidin A (16 steps) have been also accomplished for the first time.
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A unified strategy toward asymmetric divergent syntheses of nine C8-ethano-bridged diterpenoids A1-A9 (candol A, powerol, sicanadiol, epi-candol A, atisirene, ent-atisan-16α-ol, 4-decarboxy-4-methyl-GA12, trachinol, and ent-beyerane) has been developed based on late-stage transformations of common synthons having ent-kaurane and ent-trachylobane cores. The expeditious assembly of crucial advanced ent-kaurane- and ent-trachylobane-type building blocks is strategically explored through a regioselective and diastereoselective Fe-mediated hydrogen atom transfer (HAT) 6-exo-trig cyclization of the alkene/enone and 3-exo-trig cyclization of the alkene/ketone, showing the multi-reactivity of densely functionalized polycyclic substrates with πCâC and πCâO systems in HAT-initiated reactions. Following the rapid construction of five major structural skeletons (ent-kaurane-, ent-atisane-, ent-beyerane-, ent-trachylobane-, and ent-gibberellane-type), nine C8-ethano-bridged diterpenoids A1-A9 could be accessed in the longest linear 8 to 11 steps starting from readily available chiral γ-cyclogeraniol 1 and known chiral γ-substituted cyclohexenone 2, in which enantioselective total syntheses of candol A (A1, 8 steps), powerol (A2, 9 steps), sicanadiol (A3, 10 steps), epi-candol A (A4, 8 steps), ent-atisan-16α-ol (A6, 11 steps), and trachinol (A8, 10 steps) are achieved for the first time.
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Diterpenos de Tipo Kaurano , DiterpenosRESUMEN
Triacylamines with Cs symmetry have been explored in asymmetric organocatalysis, leading to the development of a novel catalytic enantioselective desymmetrization of prochiral triacylamines by methanolysis under the catalysis of chiral pseudopeptidic guanidine-guanidinium salt having a weakly coordinating anion. This organocatalytic methodology provides an effective approach to the synthetically useful chiral imide-esters with a 1,5-dicarbonyl moiety, and its synthetic potential has been manifested in the asymmetric synthesis of two GABA analogue drugs, (R)-Baclofen·HCl and (S)-Pregabalin.
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Baclofeno , Ésteres , Catálisis , Guanidina , Imidas , Pregabalina , EstereoisomerismoRESUMEN
The unique reactivity of indolyl-substituted p-QMs as a new type of two-carbon synthon has been explored for the first time in a novel iron(III)-catalyzed tandem annulation. This (2+2) annulation/retro-4π electrocyclization/imino-Nazarov cyclization cascade reaction is characterized by an unusual structural reconstruction of indolyl-substituted p-QMs, leading to an expeditious assembly of synthetically important functionalized cyclopenta[b]indoles.
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Indoles , Hierro , Catálisis , Ciclización , Indolquinonas , Indoles/químicaRESUMEN
A new tandem annulation of p-quinone methides (p-QMs) with ynamides is described. This cascade reaction features a unique combination of (2 + 2) annulation, retro-4π electrocyclization, and imino-Nazarov cyclization, wherein vinyl p-quinone methides (p-VQMs) as one of the key intermediates have been identified chemically. Significantly, an unusual structural reconstruction of p-QMs involving the cleavage of the C5-C6 bond and the late-stage formation of the C4-C6 bond is involved, leading to a methodology development for the construction of functionalized aminoindenes.
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A new hypervalent-iodine(III)-mediated tandem reaction involving oxidative dearomatization and inâ situ aziridination of phenolic amines is described, providing a mild and effective method for the assembly of structurally interesting and synthetically useful aziridines. Importantly, the densely functionalized aziridines resulting from this unprecedented tandem reaction offer a platform for expeditious access to architecturally diverse aza-heterocycles through transformations initiated by selective ring-opening of aziridines.
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An unprecedented asymmetric catalytic (4 + 2) annulation reaction of aryl-substituted γ-methylidene-δ-valerolactones (GMDVs) with isatin-derived para-quinone methides (p-QMs) has been developed under the catalysis of palladium(0) and (S,S,S)-(-)-Xyl-SKP, offering a new approach for the diastereo- and enantioselective synthesis of chiral cyclohexadienone-fused cyclohexyl spirooxindoles. Significantly, three highly congested contiguous tetrasubstituted carbon atoms embedded in bispirocyclic skeleton, of which two are vicinal quaternary stereogenic centers, are forged in an effective and selective manner (up to 99% yield, up to 95% ee, >20/1 dr). The current reaction represents the first exploration of enantioselective catalytic (4 + 2) annulation forming the six-membered carbocycles in the chemistry of both GMDVs and p-QMs.
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A novel asymmetric catalytic (2+3) annulation of p-quinone methides with CN-substituted trimethylenemethane is described under palladium catalysis, providing an alternative approach for the enantioselective construction of highly functionalized chiral spirocyclopentyl p-dienones. Driven by the significant improvement in the reactivity and enantioselectivity, a novel type of non-C2-symmetric phosphoramidite ligand from the chirality-matched combination of (S)-BINOL and sterically demanding amine derived from l-hydroxyproline is evolved and explored for the protocol presented here.
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Palladium-catalyzed asymmetric [4+5] annulation of ortho-quinone methides (o-QMs) with substituted vinylethylene carbonates (VECs) is described for the first time, giving a novel enantioselective approach to chiral nine-membered benzoheterocycles. Based on this designed [4+5] annulation, an unprecedented silica gel-promoted tandem rearrangement reaction featuring a unique asymmetric aromatic Claisen rearrangement is explored at room temperature, offering a new method for asymmetric construction of all-carbon quaternary stereocenters embedded in chiral functionalized homoallylic alcohols.
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A novel Au-catalyzed [2 + 3] annulation reaction of enamides with propargyl esters has been developed, providing a new method for expeditious assembly of synthetically useful functionalized 1-azaspiro[4.4]nonane building blocks. Based on this key annulation, strategic installation of the pivotal azaspirocyclic core, followed by constructing the benzazepine unit via Witkop cyclization, led to the divergent total syntheses of cephalotaxine and cephalezomine H.
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Lycopodium alkaloids with structural diversity and biological significance have been stimulating an increasing interest in the synthetic and medicinal communities, in which inspiration and exploration of their related biogenetic relationship generally constitute one of the major concerns. Driven by the plausible biogenetic entry to lycojaponicumin D as the first member of Lycopodium alkaloids having a structurally unusual C3-C13-linked scaffold, a new connection with lycodoline has been proposed and discovered on the basis of the design of an unprecedented bioinspired tandem fragmentation/Mannich reaction. Initiated by expeditious assembly of bridgehead heterofunctionalization in the [3.3.1] bicyclic system of lycodoline, a novel tandem palladium-mediated oxidative dehydrogenation/hetero-Michael reaction has been developed for the strain-driven formation of the C-heteroatom bond, leading to a new approach to conformationally rigid bridgehead heteroquaternary carbons. The present unified strategy provides a scenario for the divergent total syntheses of nine natural Lycopodium alkaloids and four unnatural C12 epimers, wherein (±)-lycojaponicumin D and six lycodoline-type alkaloids have been synthetically achieved for the first time.
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Alcaloides/síntesis química , Lycopodium/química , Alcaloides/química , Cristalografía por Rayos X , Ciclización , Modelos Moleculares , Estructura Molecular , EstereoisomerismoRESUMEN
An unprecedented asymmetric catalytic tandem aminolysis/aza-Michael addition reaction of spirocyclic para-dienoneimides has been designed and developed through organocatalytic enantioselective desymmetrization. A unified strategy based on this key tandem methodology has been divergently explored for the asymmetric total synthesis of two natural Apocynaceae alkaloids, (+)-deethylibophyllidine and (+)-limaspermidine. The present studies not only enrich the tandem reaction design concerning the asymmetric catalytic assembly of a chiral all-carbon quaternary stereocenter contained in the densely functionalized hydrocarbazole synthons but also manifest the potential for the application of the asymmetric catalysis based on the para-dienone chemistry in asymmetric synthesis of natural products.
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Apocynaceae/química , Productos Biológicos/síntesis química , Alcaloides Indólicos/síntesis química , Productos Biológicos/química , Carbazoles/síntesis química , Carbazoles/química , Catálisis , Alcaloides Indólicos/química , Modelos Moleculares , EstereoisomerismoRESUMEN
Cat. on a hot tin roof: Enantioselective catalytic Michael addition of α-cyanoketones to acrylates under bifunctional organocatalysis was used to construct the unique arylic all-carbon quaternary stereocenter, which is synthetically crucial in the chemical synthesis of optically pure cis-aryl hydroindole alkaloids. The protocol offers an asymmetric route to (+)-vittatine, (+)-epi-vittatine, and (+)-buphanisine.
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Alcaloides de Amaryllidaceae/síntesis química , Liliaceae/química , Fenantridinas/síntesis química , Alcaloides de Amaryllidaceae/química , Catálisis , Cristalografía por Rayos X , Conformación Molecular , Fenantridinas/química , EstereoisomerismoRESUMEN
The pain ends here: A novel synthetic strategy for the construction of (±)-morphine ringsâ B and E was developed, in which SmI2 -promoted reductive coupling/desulfurization and tandem alcoholysis/oxa-Michael addition featured as the key steps for the assembly of the C9-C14 and C5-O bonds, respectively. Asymmetric tandem alcoholysis/oxa-Michael addition was also feasible for the enantiocontrolled synthesis of morphine.