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This work reports a catalytic method that affords seven-membered carbon rings via expansion of β-ketoesters. This method tolerates alkynyl 1,2-diketones, common ynones, and alkynyl ketoesters, and affords the products with multiple functional groups.

The Nazarov cyclization has been established as a powerful tool in constructing cyclopentenone skeletons. In sharp contrast, oxa-Nazarov cyclization that affords dihydrofuranones, a new type of product, has been less explored. In this work, we report the I

Copper-catalyzed divergent annulations between α-diketones and alkynyl α-diketones have been achieved, delivering a series of highly functionalized and biologically important cis-hexahydro-2H-cyclopenta[b]furan (HCPF) and 2-hydroxydihydrofuran-3(2H)-one (HDFO) products with high levels of stereoselectivity under identical conditions. The protocol features the use of earth-abundant copper catalyst, mild conditions, shortening synthetic routes in constructing different molecular frameworks, and reducing the corresponding possible waste production. The substituents of the nucleophilic α-diketones play crucial roles in switching the reaction pathways.

Two unprecedented reactions using alkynyl 1,2-diketones and 1,3-dicarbonyls under phosphine catalysis have been achieved, furnishing a range of acyloxy allylidene malonates and γ-alkylidenebutenolides in good yields with high stereoselectivities.

We describe in this paper that using secondary OH as the kinetic resolution auxiliary group, a series of previously unavailable fluorinated fully-substituted carbon molecules can be obtained with excellent level of enantioselectivities.

Developing innovative dynamic kinetic resolution (DKR) modes and achieving the highly regio- and enantioselective semihydrogenation of unsymmetrical α-diketones are two formidable challenges in the field of contemporary asymmetric (transfer) hydrogenation. In this work, we report the highly regio- and stereoselective asymmetric semi-transfer hydrogenation of unsymmetrical α-diketones through a unique DKR mode, which features the reduction of the carbonyl group distal from the labile stereocenter, while the proximal carbonyl remains untouched. Moreover, the protocol affords a variety of enantioenriched acyclic ketones with α-hydroxy-α′-C(sp2)-functional groups, which represent a new product class that has not been furnished in known arts. The utilities of the products have been demonstrated in a series of further transformations including the rapid synthesis of drug molecules. Density functional theory calculations and plenty of control experiments have also been conducted to gain more mechanistic insights into the highly selective semihydrogenation. Nasl. z nasl. zaslona. Opis vira z dne 4. 1. 2023. Bibliografija: str. 596-598. Abstract. National Natural Science Foundation of China National Natural Science Foundation of China National Natural Science Foundation of China Research Program of the Chinese Academy of Sciences Fujian Natural Science Foundation ARRS ARRS

Four types of unprecedented and chemodivergent reactions between α-diketones and alkynyl α-diketones have been achieved under the catalysis of phosphine and Bronsted base, respectively, leading to the rapid construction of four different classes of biologically important but synthetically challenging molecular scaffolds including 2-hydroxyfuran-3(2H)-ones, 4-hydroxy-2-oxabicyclo[2.2.1]heptan-3-ones, 1,3-diaryl cyclobutanes, and 4-(furan-2(3H)-ylidene)cyclopent-2-enones. The formation of the products includes two novel rearrangement processes, and further transformations on the products can be easily achieved to deliver value-added substances such as highly functionalized cyclopentanes. Moreover, the 2-hydroxyfuran-3(2H)-one products display promising photophysical properties such as green luminescence under UV light and aggregation-induced emission effect, showing the practical application value of this work. The great potential of α-diketones in both synthetic chemistry and material science has been unambiguously demonstrated.

N-Heterocyclic carbene-catalyzed asymmetric construction of cyclopentenones using enals and α-diketones is achieved, furnishing a series of highly functionalized cyclopentenones in a highly diastereo- and enantioselective manner. The protocol tolerates substrates with both aromatic and aliphatic groups, and further transformations of the products delivered a range of value-added molecules.

The mechanism of N-heterocyclic carbene-catalyzed umpolung of β,γ-unsaturated α-diketone was studied using both density functional theory (DFT) calculations and experimental methods. In contrast to the originally proposed mechanism, the calculations revealed a more complicated process involving both nucleophilic O-acylated homoenolate and electrophilic α,β-unsaturated acyl azolium intermediates. The experimental studies confirmed the existence of the aforementioned two key intermediates. A revised mechanism has been proposed to demonstrate the detailed mechanistic insights into the product formation.

We report the highly regio- and enantioselective alkynylation of alkynyl 1,2-diketones under Lewis acid catalysis, leading to the formation of a series of biologically important 3(2H)-furanones wit...

Developing a catalytic kinetic resolution (KR) protocol affording enantioenriched α-functionalized ketones with broad substrate scope and high efficiency has been a longstanding challenge. Here, we...

The catalytic asymmetric construction of tetrasubstituted carbon stereocenters constitutes one of the most challenging research topics in organic synthesis, which further plays vital roles in diverse fields including medicinal and materials chemistry. In this context, the α-functionalization of β-ketocarbonyl compounds serves as one of the most frequently used strategies to address the issue. Compared to cyclic β-ketocarbonyls, the catalytic asymmetric α-functionalization of acyclic β-ketocarbonyls is more difficult but has gained enough progress over the last several decades. This review illustrates the recent advances in this field, including asymmetric fluorination with acyclic α-branched β-ketocarbonyl participation, Michael addition, amination, aldol reaction, α-alkylation, α-alkynylation, α-oxygenation, Mannich reaction, etc. Furthermore, a thorough survey of all these reactions indicates the existence of a general principle which is called the “Methyl Rule”. Alternative methods that can complement the deficiency of reports of the use of direct asymmetric catalysis are also presented.

Regioselectivity-switchable reactions hold irreplaceable importance in the construction of diversified architectures. In this work, Brønsted base-catalyzed regioselectivity-switchable annulations between alkynyl α-diketones and α-cyanoketones have been achieved for the first time, delivering a series of skeletally thoroughly different dihydrofurofuran and furan derivatives. A range of novel transformations of the products can be realized. The work also demonstrates the unique features of alkynyl α-diketone chemistry, which are in sharp contrast to the current understanding of ynone-related chemistry.

Inverse-electron-demand Diels-Alder reactions have attracted intense research focus. However, enolate and enamine are the most employed intermediates to realize such transformation, and the use of dienolate intermediate remains elusive. Reported herein is the asymmetric inverse-electron-demand oxa-Diels-Alder reaction between allyl ketones and alkenyl 1,2-diketones using a bifunctional thiourea catalyst. The reaction afforded various highly functionalized dihydropyrans with good to excellent enantioselectivities under mild conditions, and further novel transformations on the products have also been realized.

1,3-Diketones with quaternary stereocenters are extraordinarily useful building blocks both in academic research and industrial production. However, the access to enantiopure acyclic 2,2-disubstituted 1,3-diketones has suffered from an extremely limited substrate scope and poor stereoselectivity control. In this paper, we report the successful organocatalytic kinetic resolution of 1,3-diketones with central quaternary stereocenters through the introduction of internal nucleophiles. Two basic resolution modes were established, allowing access to a broad scope of enantioenriched 1,3-diketones with quaternary stereocenters, together with a large variety of tetralone derivatives with vicinal fully substituted carbon centers, and both of them are not easily available via currently known methods. The inherent principles between the different combinations of ketone groups and the resolution patterns were also disclosed. This work constitutes a good complementary choice for the construction of 1,3-diketones with quaternary stereogenic centers and provides insightful information for further studies on diketone substrate-mediated intramolecular annulations and kinetic resolutions.

Contemporary asymmetric catalysis faces huge challenges when prochiral substrates bear electronically and sterically unbiased substituents and when substrates show low reactivities. One of the inherent limitations of chiral catalysts and ligands is their incapability in recognizing prochiral substrates bearing similar groups. This has rendered many enantiopure substances bearing several similar substituents inaccessible. Here we report the rationale, scope, and applications of the strategy of kinetic resolution of auxiliary adjacent alcohols (KRA*) that can be used to solve the above troubles. Using this method, a large variety of optically enriched tertiary alcohols, epoxides, esters, ketones, hydroxy ketones, epoxy ketones, β-ketoesters, and tetrasubstituted methane analogs with two, three, and four spatially and electronically similar groups can be readily obtained (totally 96 examples). At the current stage, the strategy serves as the optimal solution that can complement the inability caused by direct asymmetric catalysis in getting chiral molecules with challenging fully substituted stereocenters., A large number of enantiopure substances, such as those with tetrasubstituted carbon centres bearing several similar substituents, are inaccessible due to the incapability of chiral catalysts/ligands to recognize those substrates. Here, the authors develop kinetic resolution of auxiliary adjacent alcohols (KRA*) strategy to access various optically enriched compounds with two, three or four spatially and electronically similar groups.

The mechanism of

A unique deoxygenative cyclodimerization of alkynyl 1,2-diketones facilitated by Ti(O

Bicyclo[3.2.1]octanes and related structures are unique units that widely exist in natural products, but the rapid and stereoselective construction of this skeleton is a challenging issue. We report the stereodivergent synthesis of bicyclo[3.2.1]octenes using Nazarov reagents and alkenyl 1,2-diketones with Bronsted base catalysis under mild conditions. Both stereoisomers of the bridged products can be obtained by tuning the reaction conditions, and cyclohexene product can also be selectively formed.

We report the highly regio- and enantioselective alkynylation of alkynyl 1,2-diketones under Lewis acid catalysis, leading to the formation of a series of biologically important 3(2

An unprecedented cascade annulation between alkynyl 1,2-diketones and indene-1,3-diones is achieved for the first time, leading to a series of propeller-like large conjugated compounds in ≤99% yield. The products show strong crystallization-induced emission, with the colors changing from green to red. The fluorescence of the dye can be switched on and off by external acid/alkali stimuli, which can be utilized to develop a practical technology for rewritable information storage and security ink.

The discovery of new reaction modes mediated by easily available substrates is an important research topic in organic synthesis. Allyl ketones and related compounds have been demonstrated to undergo γ- or α-selective additions to different electrophiles. We disclose here the Brønsted base-catalyzed reaction of allyl ketones and alkynyl 1,2-diketones, which undergo a unique α-selective addition/intramolecular aldol-type annulation/C-C bond cleavage process, and a series of 2-acyloxycyclopent-3-enones can be obtained under very mild conditions.

The umpolung of alkynyl 1,2-diketones via N-heterocyclic carbene (NHC) catalysis was achieved for the first time, allowing rapid access to a large variety of synthetically and pharmaceutically important α-pyrones under very mild conditions. A completely new NHC-catalyzed umpolung pattern involving an O-acylated allenolate as the key intermediate was proposed. Moreover, an unprecedented reaction pathway, featured by a series of group migrations and new bond formation, was postulated to demonstrate the formation of the products.

Organocatalyzed asymmetric Friedel–Craft reactions have enabled the rapid construction of chiral molecules with highly enantioselectivity enriching the toolbox of chemists for producing complex substances. Here, we report N-heterocyclic carbene-catalyzed asymmetric indole Friedel–Crafts alkylation-annulation with α,β-unsaturated acyl azolium as the key intermediate, affording a large variety of indole-fused polycyclic alkaloids with excellent diastereo- and enantioselectivities. The reaction mechanism is also investigated, and the reaction products can be easily converted to highly functionalized indole frameworks with different core structures. Indole-fused polycyclic alkaloids are present in numerous bioactive natural products. Here an enantioselective N-heterocyclic carbene-catalysed Friedel–Crafts alkylation/annulation cascade using acyl azolium salts as the electrophile provides access to these products with high stereoselectivity.

The resolution technique of stereodivergent reaction on racemic mixtures (stereodivergent RRM) was employed for the first time in ruthenium complex catalyzed transfer hydrogenation of racemic epoxy ketones, providing a new and very simple method that allows access to enantioenriched epoxy alcohols with three stereogenic centers in a one-step fashion. The protocol features simple reaction conditions, practical operation, ability to scale up, and broad group tolerance.

The unique antimicrobial mechanism of antimicrobials make them a promising substitute for antibiotics for fighting drug-resistant bacteria. Both melittin and thanatin have antimicrobial bioactivity. However, thanatin does not inhibit the growth of Staphylococcus aureus. Melittin can inhibit S. aureus and has strong hemolytic activity. In the present study, the mutant fragments of melittin and thanatin were combined by flexible peptides to form a novel hybrid peptide, which was synthesized based on the secondary and tertiary structure prediction. The hybrid peptide inhibited S. aureus with a hemolytic concentration of above 45 μmol/L and inhibition rate in SMMC-7721 cells of 19.14%. The hybrid antimicrobial peptide, which was designed by the combination of α-helix and β-lamellar antimicrobial peptides, showed that both types of peptides did not interact with each either on spatial structure or biological activities, thereby providing a novel idea for the design of artificial antimicrobial peptides.

Increasing effort has been made towards the asymmetric total synthesis of rotenoid natural products owing to their impressive biological and pharmaceutical activities. Here we report the modular asymmetric total synthesis of rotenoid natural products. The concise construction of the cis-fused tetrahydrochromeno[3,4-b]chromene core structure of rotenoids through N-heterocyclic carbene-catalyzed dynamic kinetic resolution is achieved, and a series of annulation products containing rotenoid key structures are rapidly assembled using this method. More importantly, the protocol enables the modular synthesis of a variety of rotenoid natural products in a highly convergent fashion, and the concise asymmetric total synthesis of tephrosin, the first asymmetric total synthesis of 12a-hydroxymunduserone, milletosin, and 12a-hydroxyrotenone, and the formal synthesis of deguelin are accomplished. Rotenoid natural products have attracted interest as synthetic targets. Here N-heterocyclic carbene-catalysed dynamic kinetic resolution is used to rapidly and enantioselectively assemble the rotenoid core, enabling the modular asymmetric total synthesis of several rotenoid natural products

The strategy of stereodivergent reactions on racemic mixtures (stereodivergent RRM) was employed for the first time in intramolecular benzoin reactions and led to the rapid access of chromanones/flavanones with two consecutive stereocenters. The easily separable stereoisomers of the products were obtained with moderate to excellent enantioselectivities in a single step. Catechol type additives proved crucial in achieving the desired diastereo- and enantioselectivities.

The stereoselectivity in the 6-exo cyclization of α-carbamoyl radicals was investigated experimentally and theoretically. The BEt3/O2-initiated iodine-atom-transfer radical cyclization reactions of substituted N-(but-3-en-1-yl)-N-(tert-butyl)-2-iodoalkanamides were carried out, which led to the predominant formations of 3,4-cis, 4,5-trans, or 4,6-trans substituted δ-lactams. Density functional calculations at the B3LYP/6-31G* level revealed that the 6-exo radical cyclization proceeds via boat-conformational transition states. Furthermore, a mechanistic insight into the stereoselectivity was provided and the calculation results were in excellent agreement with the experimental observations.

Racemic mixtures of four stereoisomers are easily formed via many fundamental organic transformations, but the direct utilities of these mixtures have been less studied and remain large challenges to date. In this work, we introduce a new method, i.e., divergent dynamic kinetic resolution, to achieve the separation of racemic mixtures of four stereoisomers. The hypothesis was proved by using a N-heterocyclic carbene-catalyzed benzoin reaction, which afforded two separable diastereomeric products bearing three consecutive stereocenters with good to excellent enantioselectivties. We believe that this resolution protocol will find applications in more transformations.

The development of cancer in patients with schizophrenia is affected by genetic and environmental factors and antipsychotic medication. Several studies found that schizophrenia was associated with decreased risk of some cancers, and the neuroleptic medication might help to reduce the risk of colorectal cancer (CRC). Phenothiazine drugs including trifluoperazine (TFP) are widely used antipsychotic drugs and showed some antitumor effects, we here investigated the potential application of TFP in the treatment of colon cancer. A series doses of TFP were treated to the colon cancer cell line HCT116 and the inhibitory concentration (IC50 ) of TFP for HCT116 was determined by cell counting kit-8. The results indicated that the treatment of TFP impaired the cell vitality of HCT116 in a dose- and time-dependent manner. Meanwhile, the Edu assay demonstrated that the proliferation was also inhibited by TFP, which was accompanied with the induction of apoptosis and autophagy. The expression of CCNE1, CDK4, and antiapoptosis factor BCL-2 was downregulated but the proapoptosis factor BAX was upregulated. The autophagy inhibitor chloroquine could significantly reverse the TFP-induced apoptosis. Moreover, the ability of migration and invasion of HCT116 was found to be suppressed by TFP, which was associated with the inhibition of epithelial-mesenchymal transition (EMT). The function of TFP in vivo was further confirmed. The results showed that the administration of TFP remarkably abrogated the tumor growth with decreased tumor volume and proliferation index Ki-67 level in tumor tissues. The EMT phenotype was also confirmed to be inhibited by TFP in vivo, suggesting the promising antitumor effects of TFP in CRC.

We report that α-acyloxy-β,γ-unsaturated cyclopentenones were used as starting substrates to make various trisubstituted cyclopentadienones. The substrates are easily available in one step from our previously developed protocol, and the potential of this cyclopentadienone formation method was demonstrated in a series of Diels–Alder reactions, forming dimerization products, dimethyl phthalate derivatives, and polyaryl benzene compounds.

The aim of this study was to investigate the effect of montmorillonite on nonylphenol (4-nonylphenol, 4-NP) enrichment in a zebrafish model. The AB strain zebrafish were used as the animal subjects, and three concentration gradients were set for both nonylphenol and montmorillonite, according to their actual concentrations in aquaculture water in Huzhou City. A group treated with nonylphenol alone was also set, adding up to 12 experimental groups. Concentrations of nonylphenol enriched in the liver, muscle and gills of zebrafish were detected by solid phase microextraction&ndash, high performance liquid chromatography at Days 7, 15 and 30, respectively. Additionally, the relative enzymatic activity of superoxide dismutase (SOD) and the glutathione S-transferase (GST) were also detected, and the data were statistically analyzed. The results showed that the concentrations of nonylphenol in zebrafish peaked at Day 7 and gradually decreased afterwards for all the experimental groups. The montmorillonite reduces short-term accumulation of nonylphenol in gills, and the high concentration of nonylphenol facilitates its enrichment in liver and muscle, while the low concentration of nonylphenol does not. Meanwhile, the low concentration of nonylphenol in liver exerts an influence on the inductive effect of SOD and GST, while the high concentration of nonylphenol shows the inhibiting effect of SOD and GST.

To investigate the effect of montmorillonite on nonylphenol enrichment in a zebrafish model. The AB strain zebrafish were used as the animal subjects and three concentration gradients were set for both nonylphenol and montmorillonite, according to their actual concentrations in aquaculture water in Huzhou city. A group treated with nonylphenol alone was also set, adding up to 12 experimental groups. Concentrations of nonylphenol enriched in the liver, muscle, and gill of zebrafish were detected by solid phase microextraction–high performance liquid chromatography at Day 7, 15, and 30, respectively. Besides, the relative enzymatic activity of Superoxide dismutase (SOD) and the Glutathione S-transferase (GST) were also been detected, and the data were statistically analyzed. The results showed that the concentrations of nonylphenol in zebrafish peaked at Day 7 and gradually decreased afterwards for all the experimental groups. And the montmorillonite reduces short-term accumulation of nonylphenol in gills, and the high concentration of nonylphenol facilitates its enrichment in liver and muscle while the low concentration of nonylphenol doesn’t. Meanwhile, the low concentration of nonylphenol in liver exerts an influence on the inductive effect of SOD and GST while the high concentration of nonylphenol shows the inhibiting effect of SOD and GST.

Sodium phenylbutyrate (SPB) as a salt of 4-phenylbutyric acid (4-PBA) has been reported to be an ammonia scavenger, histone deacetylase inhibitor, and an endoplasmic reticulum stress inhibitor in various diseases, including neurological diseases, inflammatory disorders, and carcinogenesis. Although phenylbutyrate showed effective antitumor properties in many cancers, its role in oral squamous cell carcinoma (OSCC) remains further characterized. Thus, the OSCC cell lines CAL27, HSC3, and SCC4 were treated with a series of doses of SPB for different times. The IC

The umpolung of β,γ-unsaturated diketones through N-heterocyclic carbene catalysis is described, which allows access to a variety of highly functionalized bicyclic cyclohexene-β-lactones and 1,3,4-triaryl benzenes. An unprecedented reaction pattern involving the catalytic formation of nucleophilic O-acylated homoenolate intermediate is proposed. A diverse set of transformations on the product further showed the synthetic potential of this protocol.

The highly stereoselective intermolecular all-carbon [4+2] annulation between in situ generated acyclic dienolates and α,β-unsaturated acyl azoliums is disclosed. The identification of 2-acyloxy-3-butenones as suitable diene precursors is the key to the success of this transformation. The corresponding highly functionalized cyclohexene products, which are inaccessible from Diels–Alder reactions, were delivered with high levels of diastereo- and enantioselectivities. A series of further transformations based on the product showed the potential of this reaction.