Cyclopentanone Derivatives Research Articles

Organocatalytic Activation of Unsymmetrical 2,3‐Diketones towards Catalytic Asymmetric Domino Michael–Henry Reaction

In this study, we explored a method to distinguish between both enolizable regions of unsymmetrical 2,3‐diketones in organocatalytic domino reactions involving nitroalkenes. The selective formation of an enamine from only one side of the molecule was made possible by the use of optically pure 2‐(trifluoromethyl)pyrrolidine. This catalyst, remarkably enhancing the reaction, owes its efficacy to a unique interplay between basicity and nucleophilicity. These features caused the enolization of the substrate at the second possible site to be omitted. The approach resulted in excellent regio‐ diastereo‐ and enantioselectivity (91‐99% ee) across various nitroalkenes, leading to the synthesis of novel cyclopentanone derivatives with three contiguous stereogenic center.

Hydrogen-mediated acid-base transformation of Ni supported Mo5N6 for hydrogenative rearrangement of furfural derivatives

The hydrogenative rearrangement of bioderived furfural derivatives to various cyclopentanone derivatives is vital for synthesizing fine chemicals but challenging owing to the complex cascade reaction network.

Synthesis of a New Series of Anthraquinone-Linked Cyclopentanone Derivatives: Investigating the Antioxidant, Antibacterial, Cytotoxic and Tyrosinase Inhibitory Activities of the Mushroom Tyrosinase Enzyme Using Molecular Docking.

New bioactive anthraquinone derivatives are investigated for antibacterial, tyrosinase inhibitory, antioxidant cytotoxic activity, and molecular docking. The compounds were produced using the grindstone method, yielding 69 to 89%. These compounds were analyzed using IR, 1H, and 13C NMR and elemental and mass spectral methods. Additionally, the antibacterial, antioxidant, and tyrosinase inhibitory activities of all the synthesised compounds were evaluated. Compound 2 showed remarkable tyrosinase inhibition activity, with an (IC50: 13.45 µg/mL), compared to kojic acid (IC50: 19.40 µg/mL). It also exhibited moderate antioxidant and antibacterial activities with respect to the references BHT and ampicillin, respectively. Kinetic analysis revealed that the tyrosinase inhibitory activity of compound 2 was non-competitive and competitive, whereas that of compound 1 was low. All compounds (1-8) were significantly less active than doxorubicin (LC50: 0.74±0.01μg/mL). However, compound 2 affinity for the 2Y9X protein was lower than kojic acid, with a lower docking score (-8.6 kcal/mol compared to (-4.7 kcal/mol), making it more effective. All synthesized compounds displayed remarkable antibacterial, tyrosinase inhibitory, antioxidant, and cytotoxic activities, with compound 2 showing exceptional potency as a multitarget agent. Anthraquinone substituent groups may offer the potential for the development of treatments. The derivatives were synthesized using the grindstone method, and their antibacterial, antioxidant, tyrosinase inhibitory, and cytotoxic activities were inspected. Molecular docking and molecular dynamics simulations were performed using compound 2 and kojic acid to validate the results and confirm the stability of the compounds.

Thermal decomposition behaviors and degradation kinetics of biobased polyesters with partial crosslinking to eliminate cyclic compounds

A series of poly(butylene adipate-co-butylene itaconate) (PBAPI) copolyesters with and without a small amount of ethylenediaminetetraacetic acid (EDTA) were synthesized via melt polymerization. Thermogravimetric analysis -gas chromatography/mass spectroscopy (TGA-GC/MS) techniques were used to identify the thermal degradation behaviors. By introducing 0.1 mol % EDTA into BA/BI = 10/0, the dominant degradation product was converted from furan and cyclopentanone derivatives to CO2 and formation of cyclic compounds was notably inhibited. Moreover, similar tendencies were observed when the BI content increased, demonstrating that the existence ratio of CO2 and furan derivatives increased while the concentrations of cyclopentanone and cyclic compounds reduced during decomposition. Finally, no cyclic compound product was detected in the BA/BI = 7/3 copolyester. These results indicate that the introduction of both EDTA and BI inhibits generation of cyclic compounds, which are attributed to the formation of partial crosslinking for chemical structures. The nonisothermal degradation kinetic was also carried out to investigate the decomposition behaviors. The activation energy requirements at each degradation stage varied with the composition of BA/BI ratios and the introduction of EDTA, demonstrating further evidence of degradation behavior transformation.

A Comprehensive Review on Metal Catalysts for the Production of Cyclopentanone Derivatives from Furfural and HMF.

The catalytic transformation of biomass-based furan compounds (furfural and HMF) for the synthesis of organic chemicals is one of the important ways to utilize renewable biomass resources. Among the numerous high-value products, cyclopentanone derivatives are a kind of valuable compound obtained by the hydrogenation rearrangement of furfural and HMF in the aqueous phase of metal-hydrogen catalysis. Following the vast application of cyclopentanone derivatives, this reaction has attracted wide attention since its discovery, and a large number of catalytic systems have been reported to be effective in this transformation. Among them, the design and synthesis of metal catalysts are at the core of the reaction. This review briefly introduces the application of cyclopentanone derivatives, the transformation mechanism, and the pathway of biomass-based furan compounds for the synthesis of cyclopentanone derivatives. The important progress of metal catalysts in the reaction since the first report in 2012 up to now is emphasized, the characteristics and catalytic performance of different metal catalysts are introduced, and the critical role of metal catalysts in the reaction is discussed. Finally, the future development of this transformation process was prospected.

The importance of constructing Triple-functional Sr2P2O7/Ni2P catalysts for smoothing hydrogenation Ring-rearrangement of Biomass-derived Furfural compounds in water

Rational design of catalysts with multi-function was of great importance for speeding mechanism-complicated heterogeneous reaction. Herein, a series of Sr-Ni-P catalysts characterized in (Sr2P2O7)m/Ni2P composite structure (Sr:Ni molar ratio m = 0.15–0.60) were prepared and investigated for hydrogenation ring-rearrangement of four biomass-derived Furfural compounds (FALs) to their Cyclopentanone derivatives (CPOs) in water. By properly manipulate m at 0.40, the superior and reproducible CPOs yields up to 96% were achieved under mild conditions in particular under low-pressure (0.1 MPa) H2. Chemical adsorption measurements disclosed that the attachment of Sr2P2O7 with Ni2P in nanoscale was crucial to construct triple-functional catalytic interface with modulated hydrogen activation (7.5–47.4 µmol/g), acid (196.4–327.3 µmol/g) and base (108.0–214.5 µmol/g) sites. H2-D2 exchange, H2-IR experiments and DFT simulation implied that H2 could be activated through heterolytic dissociation on Sr2P2O7 to participate in reaction; H218O, D2O, D2 isotope-label tracing experiments and DFT mechanism calculation further clarified that besides of H2, H2O was also frequently present in hydrogenation, ring opening, rearrangement and ring re-closing steps and acted as dual donors to provide H and O for CPO; in the favorable thermodynamic feature, a new pathway (with unsaturated dicarbonyl compound as key intermediate) achieved on Sr2P2O7/Ni2P was demonstrated to be more feasible than the reported pathway. The importance of the triple-functional Sr2P2O7/Ni2P catalytic interface for smoothing the aqueous hydrogenation transformation, in particular the function of base site for speeding the transformation was illustrated and discussed.

Release of Volatile Cyclopentanone Derivatives from Imidazolidin-4-One Profragrances in a Fabric Softener Application

Imidazolidin-4-ones were investigated as hydrolytically cleavable profragrances to increase the long-lastingness of perfume perception in a fabric softener application. The reaction of different amino acid amides with 2-alkyl- or 2-alkenylcyclopentanones as the model fragrances to be released afforded the corresponding bi- or tricyclic imidazolidin-4-ones as mixtures of diastereoisomers, which were separated by column chromatography. In polar solution, the different stereoisomers equilibrated under thermodynamic conditions to form mixtures with constant isomeric distributions, as shown by NMR spectroscopy. Dynamic headspace analysis on dry cotton demonstrated the controlled fragrance release from the precursors in practical application. Under non-equilibrium conditions (continuous evaporation of the fragrance) and depending on the structure and stereochemistry of the profragrances, the recorded headspace concentrations of the fragrance released from the precursors increased by a factor of 2 up to 100 with respect to the unmodified reference. Prolinamide-based precursors released the highest amount of fragrance and were thus found to be particularly suitable for prolonging the evaporation of cyclopentanone-derived fragrances on a dry cotton surface.

Cyclopentanone Derivative Attenuates Memory Impairment by Inhibiting Amyloid Plaques Formation in the 5xFAD Mice.

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder. This study was designed to investigate the effects of cyclopentanone derivative i.e., 2-(hydroxyl-(3-nitrophenyl)methyl)cyclopentanone (3NCP) on behavior, amyloid β (Aβ) plaque deposition, and βAPP cleaving enzyme-1 (BACE-1) expression in the 5xFAD mouse brain. In this study, computational studies were conducted to predict the binding mode of the 3NCP with target sites of the β-secretase. In vivo studies were performed on the 5xFAD mice model of AD using different behavioral test models like light/dark box, elevated plus maze (EPM), and the Barnes maze tests for the assessment of anxiety, spatial learning and memory. The thioflavin-S staining, immunohistochemistry (IHC), and RT-PCR studies were carried out to find the effect of the 3NCP on the β-amyloid plaques formation and BACE-1 expression. The results of the computational studies showed that the 3NCP has excellent binding affinities for beta-secretase. The light/dark box study depicted that the 3NCP does not cause anxiety. The 3NCP treatment effects in the EPM and Barnes maze tests showed a significant effect on learning and memory. Furthermore, the results of the thioflavin staining and IHC revealed that the 3NCP significantly reduced the formation of the beta-amyloid plaques in brain tissues. Moreover, the RT-PCR study showed that 3NCP significantly reduced the BACE-1 expression in the brain. Conclusively, the results of the current study demonstrate that the 3NCP may be a potential candidate for AD treatment in the future.

HFIP-Catalyzed Difluoroalkylation of Propargylic Alcohols to Access Tetrasubstituted Difluoroalkyl Allenes.

A hexafluoroisopropanol (HFIP)-catalyzed difluoroalkylation of propargylic alcohols with difluoroenoxysilanes to access structurally diverse tetrasubstituted difluoroalkyl allenes has been developed. This convenient procedure enables the rapid construction of highly functionalized multisubstituted fluorinated allenes in a mild and straightforward way. Furthermore, the synthetic potential of this methodology has been demonstrated by the facile synthesis of various structurally interesting fluorine-containing molecules such as gem-difluorosubstituted dihydropyran, tetrasubstituted CF2H-allene, and multisubstituted fluorinated cyclopentanone derivatives.

5-Bis-(2,6-difluoro-benzylidene) Cyclopentanone Acts as a Selective 11β-Hydroxysteroid Dehydrogenase one Inhibitor to Treat Diet-Induced Nonalcoholic Fatty Liver Disease in Mice

Background: 11β-Hydroxysteroid dehydrogenase one is responsible for activating inert glucocorticoid cortisone into biologically active cortisol in humans and may be a novel target for the treatment of nonalcoholic fatty liver disease. Methods: A series of benzylidene cyclopentanone derivatives were synthesized, and the selective inhibitory effects on rat, mouse and human 11β-hydroxysteroid dehydrogenase one and two were screened. The most potent compound [5-bis-(2,6-difluoro-benzylidene)-cyclopentanone] (WZS08), was used to treat nonalcoholic fatty liver disease in mice fed a high-fat-diet for 100 days. Results: WZS08 was the most potent inhibitor of rat, mouse, and human 11β-hydroxysteroid dehydrogenase 1, with half maximum inhibitory concentrations of 378.0, 244.1, and 621.1 nM, respectively, and it did not affect 11β-hydroxysteroid dehydrogenase two at 100 μM. When mice were fed WZS08 (1, 2, and 4 mg/kg) for 100 days, WZS08 significantly lowered the serum insulin levels and insulin index at 4 mg/kg. WZS08 significantly reduced the levels of serum triglycerides, cholesterol, low-density lipoprotein, and hepatic fat ratio at low concentration of 1 mg/kg. It down-regulated Plin2 expression and up-regulated Fabp4 expression at low concentration of 1 mg/kg. It significantly improved the morphology of the non-alcoholic fatty liver. Conclusion: WZS08 selectively inhibits rat, mouse, and human 11β-hydroxysteroid dehydrogenase 1, and can treat non-alcoholic fatty liver disease in a mouse model.

Attenuation of Spatial Memory in 5xFAD Mice by Halting Cholinesterases, Oxidative Stress and Neuroinflammation Using a Cyclopentanone Derivative.

Alzheimer’s disease (AD) is an irreversible and chronic neurological disorder that gradually destroys memory and thinking skills. The research study was designed to investigate the underlying molecular signaling involved in the neuroprotective effects of cyclopentanone derivative i.e., 2-(hydroxyl-(3-nitrophenyl)methyl)cyclopentanone (3NCP) as a therapeutic agent for AD. In this study, In vivo studies were carried out on a well-known 5xFAD mice model using different behavioural test models such as open field, rotarod, Morris water maze (MWM), and Y-maze tests. Furthermore, in vitro cholinesterase inhibition activity assays were carried out. The frontal cortex (FC) and hippocampus (HC) homogenates were tested for the levels/activities of cholinesterases, glutathione (GSH), glutathione S-transferase (GST), and catalase. Furthermore, the hippocampal expression of inflammatory cytokines was observed via RT-PCR and western blot. The results of in vivo studies show an enhancement in the learning behavior. The 3NCP treatment reduced latency time in MWM and Y-maze tests, also increase spontaneous alternation indicate significant effect of 3NCP on memory. Furthermore, open field and rotarod studies revealed that 3NCP does not cause motor coordination deficit. The results of the in vitro studies revealed that the IC50 values of the 3NCP against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were 16.17 and 20.51 µg/mL, respectively. This decline in AChE and BChE was further supported by ex vivo studies. Further, the 3NCP mitigates the GSH level, GST, and catalase activities in HC and FC. The mRNA and protein expression of inflammatory cytokines (IL-1β, IL-6, TNF-α) markedly declined in RT-PCR and western blotting. The results of the current study conclusively demonstrate that 3NCP reduces oxidative stress and mitigates neuroinflammation in 5xFAD mice, implying that 3NCP may be a potential therapeutic candidate for AD treatment in the future.

An efficient synthesis of benzylidene-2-alkoxy-4-aryl-2,3-cycloalkenopyridine-3-carbonitrile derivatives

An efficient procedure for the synthesis of a novel class of benzylidene-2-alkoxy-4-aryl-6,7-dihydro-5H-cyclopenta[b]pyridine-, -5,6,7,8-tetrahydroquinoline and/or -6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-3-carbonitrile was introduced through the one-pot multi-component reaction of cyclopentanone, cyclohexanone, and/or cycloheptanone with different aromatic aldehydes and malononitrile. The same products were also produced by classical route by the two-component reaction of dibenzylidine cyclopentanone, cyclohexanone, and/or cycloheptanone derivatives with malononitrile. The reactions were achieved using sodium alkoxide solution as catalyst and reagent.

Synthesis of Unsaturated Spiroacetals, Cyclopentanone Derivatives, in the Presence of Natural Aluminosilicate Modified with Zirconium Cations

Conditions for the condensation of cyclopentanone and n-valeric aldehyde to 2-pentylidenecyclopentanone in the presence of an alcoholic solution of piperidine have been developed. The isomerization of the latter in a continuous-flow system over γ-Al2O3 yields 2-pentylcyclopent-2-en-1-one. The condensation of the obtained unsaturated ketones with ethane-1,2-diol in the presence of a heterogeneous catalyst, a natural aluminosilicate (perlite) modified with zirconyl sulfate, has been studied. The optimum conditions for the preparation of the corresponding unsaturated spiroacetals have been found. The synthesized compounds can be used as synthetic fragrances for different purposes.

Ruthenium-catalyzed ring-opening reaction of a 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with amines — an unexpected mode of ring-opening

The ruthenium-catalyzed ring-opening reaction of a 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with amines was investigated. In the presence of an amine and a ruthenium catalyst, the N–O bond is cleaved, forming a ring-opened allylic alcohol product. Through a possible ruthenium-catalyzed redox isomerization, the allylic alcohol is transformed into a saturated carbonyl product. This unexpected mode of ruthenium-catalyzed ring-opening reaction of a 3-aza-2-oxabicyclo[2.2.1]hept-5-ene leads to the formation of a cyclopentanone derivative in moderate yields.

Synthesis of Fluoromethyl‐Substituted Cyclopentanones via Radical Fluorination and 1,2‐Alkyl Migration Cascade of Alkenyl Cyclobutanols

AbstractA radical fluorination/1,2‐alkyl migration cascade process of alkenyl cyclobutanols was developed in this study. This approach provides a mild and convenient access to the synthesis of fluoromethyl‐substituted cyclopentanone derivatives from the coupling reaction of alkenyl cyclobutanols with Selectfluor as the fluorine radical source.

Bio-based building blocks from 5-hydroxymethylfurfural via 1-hydroxyhexane-2,5-dione as intermediate.

The limits to the supply of fossil resources and their ever increasing use forces us to think about future scenarios for fuels and chemicals. The platform chemical 5-hydroxymethyl-furfural (HMF) can be obtained from biomass in good yield and has the potential to be converted in just a few steps into a multitude of interesting products. Over the last 20 years, the conversion of HMF to 1-hydroxyhexane-2,5-dione (HHD) has been studied by several groups. It is possible to convert HMF into HHD by hydrogenation/hydrolytic ring opening reaction in aqueous phase using various heterogeneous and homogeneous catalysts. This review addresses both the state of the art of HHD synthesis, including mechanistic aspects of its formation, as well as the recent progress in the application of HHD as a building block for many useful chemicals including pyrroles, cyclopentanone derivatives and triols.

Reversible intramolecular Dieckmann-type condensation of 2-(2-hydroxymethyl-5,5,6-trimethoxytetrahydropyran-3-ylcarbonyl)-cyclopentanone: an alternative access to medium-sized lactones

Levoglucosenone-derived 2-[(2S,3S,6S)-2-hydroxymethyl-5,5,6-trimethoxytetrahydro-2H-pyran-3-ylcarbonyl]cyclo-pentanone upon boiling in benzene in the presence of NaH undergoes the retro-Dieckmann-type reaction to afford 10-membered lactone, while storing this reaction mixture at room temperature brings about the starting cyclopentanone derivative. Several structurally analogous compounds were examined in respect of similar transformations.

Strategies and limitations associated with in vitro characterization of vitamin D receptor activators

In vitro cell-based assays are common screening tools used for the identification of new VDR ligands. For 25-hydroxyvitamin D3 [25(OH)D3] and 1α-hydroxyvitamin D3 [1α(OH)D3], protein expressions of CYP2R1 and CYP27B1, respectively, that form the active 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] ligand were detected in human embryonic kidney (HEK293) cells expressing the GAL4-hVDR, the human brain microvessel endothelial (hCMEC/D3) and adenocarcinoma colonic (Caco-2) cells. The impact of bioactivation enzymes was shown upon the addition of ketoconazole (10 μM KTZ), a pan-CYP inhibitor, which reduced the apparent potency of 25(OH)D3 and increased the EC50 from 272 to 608 nM in HEK293 cells. EIA assays verified that 1,25(OH)2D3 was formed and contributed to VDR activity independently of its precursors. In hCMEC/D3 cells where enzyme protein levels were lowest, changes in MDR1/P-gp expression with KTZ were minimal. In Caco-2 cells, the induction of TRPV6 (calcium channel), CYP24A1, CYP3A4, OATP1A2 and MDR1 mRNA expression was 1,25(OH)2D3 > 1α(OH)D3 > 25(OH)D3, with the magnitude of change being blunted by KTZ. Upon inclusion of KTZ in the cell-based assays, high transcriptional activities were observed for synthetic VDR activators from Teijin Pharma. Cyclopentanone derivatives: TPD-003, TPD-005, TPD-006, TPD-008 and TPD-009 (EC50s 0.06 to 67 nM, unchanged with KTZ) were found more potent over straight chain and lactone derivatives (antagonists). Most TPD compounds activated OATP1A2, CYP24A1, CYP3A4, and MDR1 (28–67%) and TRPV6 transcriptionally in Caco-2 cells. The results identified that cell-based assays with added KTZ could accurately identify new VDR activators, although these may be hypercalcemic with strong TRPV6 inducing properties.

Visible light photoredox-catalyzed difluoromethylation and ring expansion of 1-(1-arylvinyl)cyclobutanols

A visible light photoredox-catalyzed difluoromethylation and ring expansion via 1,2-carbon migration of 1-(1-arylvinyl)cyclobutanol derivatives has been developed. This approach offers a facile way to prepare difluoromethyl-substituted cyclopentanone derivatives.

An uncommon multicomponent reaction involving nucleophilic heterocyclic carbenes: facile synthesis of fully substituted cyclopentanones

An unprecedented three component reaction involving arylidene oxazolone, enal and NHC, leading to the synthesis of fully substituted cyclopentanone derivatives with three contiguous stereocenters, is reported.