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The synthesis of tetraarylmethanes has long been a challenge in the field of synthetic chemistry. In this study, a series of tetraarylmethanes were successfully synthesized through the formal nucleophilic substitution reaction of indol-2-yl diaryl methanol catalyzed by Brønsted acid. The key success of this study lies in suppressing the influence of water molecules by forming hydrogen bonds with the TFE solvent. This process leads to the formation of active 2-indole imine methide (2-IIM) intermediates, ensuring the successful synthesis of tetraarylmethanes. Furthermore, some of the products also exhibited potential anticancer activity.
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Palladium-catalyzed dipolar cycloaddition reactions represent an efficient strategy for the construction of cyclic compounds, with the development of novel dipolar precursors being a key focus. In this study, a new type of dipolar precursor was synthesized through the assembly of the vinylethylene carbonate unit and the tetrahydronaphthalene skeleton. This dipolar precursor can undergo [3 + 2], [5 + 4], and [5 + 2] cycloaddition reactions, leading to the construction of tetrahydronaphthalene-fused oxazolidin-2-ones, 1,5-oxazonines, and tetrahydrooxepines. In general, all of these reactions exhibited good reaction efficiency and functional group tolerance.
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The utilization of drone technology thrives in diverse domains, including aviation, military operations, and logistics. The pervasive adoption of this technology aims to enhance efficiency while mitigating hazards and expenditures. In complex contexts, the governing parameters of uncrewed aerial vehicles (UAV) require real-time adjustments for flight safety and efficacy. To improve the attitude estimation accuracy, this article introduces a ATT-Bi-LSTM framework for optimizing UAVs through adaptive parameter control, which integrates the state information gleaned from communication signals. The ATT-Bi-LSTM achieves data feature extraction by means of a two-layer Bidirectional Long Short-Term Memory (BI-LSTM) at its inception to enhance the feature. Subsequently, it harnesses the attention mechanism to amplify the LSTM network's output, thereby enabling the optimal control of UAV positioning. During the empirical phase, we employ optical system data for the comparative validation of the model. The outcomes underscore the commendable performance of the proposed framework in this study, particularly with regard to the three pivotal position indicators: yaw, pitch, and roll. In the comparison of indicators such as RMSR and MAE, the proposed model has the lowest error, which provides algorithm support and important reference for future UAV optimization control research.
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Despite the enormous developments in the asymmetric transformations of indole imine methides (IIMs), the remote asymmetric induction involving IIMs remains challenging due to the spatial interaction requirement between the substrate and catalyst. Herein we report the first catalytic asymmetric nucleophilic addition to indole imine 5-methide (5-IIM), the only topological isomer of IIMs whose asymmetric addition remains unknown. Despite the challenging remote stereocontrol, high efficiency and respectable enantioselectivity were achieved to provide access to a range of enantioenriched indole-containing triaryl alkanes.
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Demonstrated here is an asymmetric nucleophilic addition via primary activation of para-quinone methides (p-QMs) based on a chiral phosphoric acid catalytic system. In sharp contrast to previous CPA-based bifunctional activation processes that all required the nucleophiles to have an effective hydrogen bond donor unit (e.g., OH, NH), here no such unit is required in the nucleophile. N-protected indole nucleophiles were successfully utilized for the synthesis of chiral tetraarylmethanes with high efficiency and enantioselectivity under mild conditions. Therefore, this protocol significantly expanded the scope of asymmetric transformations of p-QMs.
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Herein we employed ethynylethylene carbonates (EECs) to achieve formal [4 + 1] and [3 + 3] cycloaddition with cyclic 1,3-dicarbonyl compounds. On one hand, EECs with styryl substitution could undergo a remotely controlled enantioselective [4 + 1] cycloaddition reaction. This reaction exhibits good chemoselectivity, regioselectivity, and enantioselectivity. In addition, a [3 + 3] cycloaddition reaction of EECs with cyclic 1,3-dicarbonyl compounds was also achieved, leading to a series of 4H-pyrans with impressive chemoselectivity and enantioselectivity.
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Direct arylation of the benzylic C(sp3)-H bond is one of the most straightforward strategies for the construction of multi-aryl methanes, owing to the extraordinary step and atom economy. In this paper, we developed the first metal-free arylation of the C(sp3)-H bond in 3-methylindoles, thereby providing rapid access to a range of diaryl- and triarylmethanes with two indole rings. Mechanistically, 3-indole imine methide serves as the key intermediate. Water plays a crucial role in this process, likely serving as a proton shuttle to facilitate the key 1,3-proton transfer step in this reaction and, thus, enhance the reaction efficiency.
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The construction of medium-sized ring compounds has been a prominent research area in synthetic chemistry. In this study, we developed a tandem strategy that combines allylic amination and ring-opening of oxetanes to synthesize medium-sized heterocycles. Specifically, N-aryl oxetan-3-amines undergo allylic amination with zwitterionic π-allylpalladium, followed by intramolecular ring-opening, resulting in the formation of medium-sized heterocycles. Notably, we are able to achieve the synthesis of 7-8 membered heterocycles with moderate to good yields by employing different types of zwitterionic π-allylpalladium species.
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Based on a halopalladation strategy, we successfully developed a haloesterification reaction of propargylic amides to synthesize a diverse range of 5-(halomethylene)oxazolidine-2,4-diones. This reaction demonstrates good yield and compatibility with various functional groups. Notably, the halogen atoms present in the resulting products can be readily substituted by other functional groups, highlighting the versatility and appeal of this method. Additionally, we have achieved the successful cyclizative dimerization of propargylic amides to produce bisoxazolidine-2,4-dione derivatives.
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The zwitterionic π-allylpalladium species, also known as dipoles, are important synthons widely used in various reactions including cycloaddition and allylic substitution. This study reported the development of a new indole-fused zwitterionic π-allylpalladium precursor compound and its application in [4 + 2] cycloaddition and allylic substitution reactions. As a result, the synthesis of pyrrolo[3,2,1-ij]quinazolin-3-one and 7-vinyl indole compounds was achieved with moderate to good yields. Notably, the allylic substitution reaction exhibited excellent regio- and stereoselectivity.
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BACKGROUND: Cancer stem cells (CSCs) play a key role in tumor cell growth, drug resistance, recurrence, and metastasis. Proanthocyanidins (PC) is widely existed in plants and endowed with powerful antioxidant and anti-aging effects. Interestingly, recent studies have found that PC exhibits the inhibitory effect on tumor growth. However, the role of PC in CSCs of colorectal cancer (CRC) and molecular mechanism remain unclear. METHODS: CCK-8, colony, and tumorsphere formation assay were used to evaluate cancer cell viability and stemness, respectively. Western blotting was used to detect the protein expression. Tumor xenograft experiments were employed to examine the tumorigenicity of CRC cells in nude mice. RESULTS: PC decreased the proliferation of CRC cells (HT29 and HCT-116), and improved the sensitivity of CRC cells to oxaliplatin (L-OHP), as well as inhibited tumor growth in nude mice. Further studies showed that PC also down-regulated CSCs surface molecular and stemness transcriptional factors, while suppressed the formations of tumorspheres and cell colony in CRC. In addition, PC-impaired proteins expressions of p-GSK3ß, ß-catenin and DVL1-3. LiCl, an activator of the Wnt/ß-catenin signaling, rescued PC-induced downregulation of CSCs markers, and reduction of tumorspheres and cell colony formation abilities in CRC cells. Furthermore, the effects of PC on inhibiting cell proliferation and enhancing L-OHP sensitivity were impaired by LiCl. CONCLUSIONS: PC exerted an inhibitory effect on CSCs via Wnt/ß-catenin in CRC, and may be a potential new class of natural drug for CRC treatment.
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Neoplasias Colorrectales , Proantocianidinas , Animales , Ratones , Humanos , Línea Celular Tumoral , Ratones Desnudos , Proantocianidinas/farmacología , Proantocianidinas/metabolismo , Proantocianidinas/uso terapéutico , beta Catenina/metabolismo , Neoplasias Colorrectales/genética , Células Madre Neoplásicas/metabolismo , Proliferación Celular , Regulación Neoplásica de la Expresión GénicaRESUMEN
A tandem allylic amination/oxa-Michael addition of vinyl methylene cyclic carbonates (VMCCs) has been developed to construct heterocycles by single palladium catalysis or palladium-organo relay catalysis. In this process, the bisnucleophiles first underwent regioselective allylic amination, and then the second nucleophilic group further completed the hetero-Michael addition reaction to form a series of heterocycles. Among them, the chiral 3,4-dihydro-2H-benzo[b][1,4]oxazines could be produced in medium to high yield with good enantioselectivity under a palladium-organo relay catalysis.
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Ligand-directed divergent synthesis (LDS) is an important synthetic tool for the preparation of structurally diverse organic molecules without tedious steps to modify substrates. Herein, we introduce the realization of 3,4-, 1,2-, and 1,4-cyclization of benzo[d]isothiazole-1,1-dioxide-fused azadienes (BDAs) through LDS, leading to tetrahydro-2H-pyrans, oxazinanes, and tetrahydro-2H-1,5-oxazocines, respectively. Using phosphinooxazoline (PHOX) ligands, we have developed a [4 + 2] cycloaddition between BDAs and substituted 2-alkylidenetrimethylene carbonates, providing access to multi-substituted chiral tetrahydro-2H-pyrans in good yields with excellent enantio-, diastereo-, and regioselectivities.
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Paladio , Piranos , Catálisis , Reacción de Cicloadición , Ligandos , Piranos/química , EstereoisomerismoRESUMEN
Colorectal cancer (CRC) is a common tumor with high morbidity and mortality. The use of oxaliplatin (L-OHP) as a first-line treatment for CRC is limited due to chemoresistance. Growing evidence have revealed that the existence of cancer stem-like cells (CSLCs) is one of the important reasons for drug resistance and recurrence of cancers. Dihydroartemisinin (DHA), a derivative of artemisinin, has showed anticancer effects on a variety of malignancies, in addition to its antimalarial effects. However, the effect and mechanism of DHA on CSLCs and chemosensitivity in CRC cells remains unclear. In this study, we found that DHA inhibited cell viability in HCT116 and SW620 cells. Moreover, DHA decreased cell clonogenicity, and improved L-OHP sensitivity. Furthermore, DHA treatment attenuated tumor sphere formation, and the expressions of stem cell surface marker (CD133 and CD44) and stemness-associated transcription factor (Nanog, c-Myc, and OCT4). Mechanistically, the present findings showed that DHA inhibited of AKT/mTOR signaling pathway. The activation of AKT/mTOR signaling reversed DHA-decreased cell viability, clonogenicity, L-OHP resistance, tumor sphere, and expressions of stemness-associated protein in CRC. The inhibitory effect of DHA on tumorigenicity of CRC cells has also been demonstrated in BALB/c nude mice. In conclusion, this study revealed that DHA inhibited CSLCs properties in CRC via AKT/mTOR signaling, suggesting that DHA may be used as a potential therapeutic agent for CRC.
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Neoplasias Colorrectales , Proteínas Proto-Oncogénicas c-akt , Animales , Ratones , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Ratones Desnudos , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Células Madre Neoplásicas , Línea Celular Tumoral , Proliferación CelularRESUMEN
While asymmetric insertion of metal carbenes into H-X (X = C, N, O, etc.) bonds has been well-established, asymmetric control over free carbenes is challenging due to the presence of strong background reactions and lack of any anchor for a catalyst interaction. Here we have achieved the first photo-induced metal-free asymmetric H-X bond insertion of this type. With visible light used as a promoter and a chiral phosphoric acid used as a catalyst, α-diazoesters and aryl amines underwent smooth N-H bond insertion to form enantioenriched α-aminoesters with high efficiency and good enantioselectivity under mild conditions. Key to the success was the use of DMSO as an additive, which served to rapidly capture the highly reactive free carbene intermediate to form a domesticated sulfoxonium ylide.
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An organocatalytic enantioselective formal hydroarylation of 2-vinyl indoles for the preparation of enantioenriched 2,3'-bis(indolyl)methanes bearing an all-carbon quaternary stereocenter is described. This reaction features mild conditions, low catalyst loading, excellent efficiency and enantioselectivity. The obtained products showed promising anticancer activity.
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Efficient Ni/(S,S)-Ph-BPE-catalyzed asymmetric hydrogenation of α-substituted α,ß-unsaturated phosphine oxides/phosphonates/phosphoric acids has been successfully developed, and a wide range of chiral α-substituted phosphines hydrogenation products were obtained in generally high yields with excellent enantioselective control (92%-99% yields, 84%->99% ee). This method features a cheap transition metal nickel catalytic system, high functional group tolerance, wide substrate scope generality, and excellent enantioselectivity. A plausible catalytic cycle was proposed for this asymmetric hydrogenation according to the results of deuterium-labeling experiments.
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An efficient cascade approach for the construction of nitrogen-containing polycyclic compounds from amines tethered with an alkenyl (or alkynyl) group and divinyl carbonates is described. In the presence of Pd(0)-catalyst, an active zwitterionic allylpalladium species is generated and undergoes allylic amination with various amines followed by Diels-Alder reaction to form various polycyclic N-heterocyclic products, including hydrophenanthridines, hydrobenzo[c]azepines (hydro)isoindoles and hydrobenzo[cd]indoles.
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Aminas , Aminación , Reacción de Cicloadición , Estructura Molecular , CatálisisRESUMEN
A new approach for the synthesis of 9-membered N,N,O-heterocycles by Pd-catalyzed [6+3] dipolar cycloaddition of N-iminoisoquinolinium ylides and 2-vinyl oxetanes has been developed. The scope of this cycloaddition was demonstrated with 28 examples. This is another important synthetic strategy for medium-sized rings by employing N-iminoisoquinolinium ylides as ternary synthons.
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Paladio , Catálisis , Reacción de CicloadiciónRESUMEN
We have developed a catalytic asymmetric allylic substitution/isomerization process with central chirality transposition. This process takes advantage of the ambident reactivity of the 2-indole imine methide generated in situ from racemic tertiary indolylmethanols. The use of a suitable chiral phosphoric acid catalyst and an ortho-directing group allowed regioselective formation a C-C bond at the 3 position but enantiocontrolled construction of a stereogenic center at the 2-benzylic position.