Cyclopentane Derivatives Research Articles

Calcium(II)‐Catalyzed Synthesis of Sulfoximinocyclopentenones

A series of 4‐sulfoximinocyclopent‐2‐en‐1‐ones were prepared in 35 to 99% yield through a calcium(II)‐catalyzed aza‐Piancatelli reaction, including in enantioenriched form. Depending on their substitution pattern, diverse diastereoselective chemical transformations can be applied to these scaffolds, allowing access to cyclopentane derivatives. This study opens synthetic routes to cyclopentane‐based scaffolds and also paves the way for the exploration of the associated chemical space in drug discovery.

Investigation of cholinesterase and α-glucosidase enzyme activities, and molecular docking and dft studies for 1,2-disubstituted cyclopentane derivatives with phenyl and benzyl units.

Six known products (4-9) were prepared from reaction of adipoyl chloride with 1,2,3-trimethoxybenzene according to the literature. From (2,3,4-trimethoxyphenyl)(2-(2,3,4-trimethoxyphenyl)cyclopent-1-en-1-yl)methanone (4) of them, four new 1,2-disubstituted cyclopentane derivatives (10-13) with phenyl and benzyl units were synthesized by reactions such as hydrazonation, catalytic hydrogenation and bromination. The obtained compounds 4-13 were examined for their in vitro inhibitory activity against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase enzymes. All compounds 4-13 showed inhibition at nanomolar level with Ki values in the range of 45.53 ± 7.35-631.96 ± 18.88nM for AChE, 84.30 ± 9.92-622.10 ± 35.14nM for BChE, and 25.47 ± 4.46-48.87 ± 7.33 for α-Glu. In silico molecular docking studies of the potent compounds were performed in the active sites of AChE (PDB: 1E66), BChE (PDB: 1P0I), and α-glucosidase (PDB: 5ZCC) to compare the effect of bromine atom on the inhibition mechanism. The optimized molecular structures, HOMO-LUMO energies and molecular electrostatic potential maps for the compounds were calculated by using density functional theory with B3LYP/6-31 + G(d,p).

Silver nanoparticles biosynthesis from Ficus pomifera, Strobilanthes flaccidifoliuss, and Crassocephalum crepidioides plant extracts

This research can potentially impact the silver nanoparticle synthesis field significantly. The study describes the synthesis and tentative mechanism involved in silver nanoparticles with bioactives compounds 1, 2, 3, and 4 (cyclopentane derivative, polyol, Indigo, and polymer), characterized isolates from Ficus pomifera Wall, Strobilanthes flaccidifolius Nees and Crassocephalum crepidioides (Benth.) Moore. The findings of this research, particularly the characterization of silver nanoparticles formed with three compounds using energy-dispersive X-ray analysis, X-ray diffraction, transmission electron microscopy, FTIR, and UV–Vis spectroscopy, could pave the way for future advancements in the field. The average size was reported to be 50 nm, 16 nm, and 61 nm, respectively, for compounds 1, 3, and 4. Tentative mechanisms were developed for the formation of the nanoparticles by each compound 1, 3, and 4. Compound 1 reduced silver after dehydration, evident from a new ester carbonyl peak at 1743 nm from the IR spectrum. Compound 2 failed to reduce silver ions.

Nickel-Catalyzed Alkene Isomerization to Access Bench-Stable Enamines and Their [3 + 2] Annulation.

Enamines are difficult to prepare on the bench due to their instability, which results in side reactions, decompositions, poor yields, etc. Herein, we developed a simple and effective method for making bench-stable enamines using a very low amount of nickel catalyst loading. The deuterium exchange, competitive reaction, and radical clock experiment have all been found to favor the ionic mechanism of this alkene isomerization. Scale-up and [3 + 2] annulation reaction of enamines with activated cyclopropane to deliver cyclopentane derivatives have shown the value of this method in organic synthesis.

Vinylcyclopropane-Cyclopentene (VCP-CP) Rearrangement Enabled by Pyridine-Assisted Boronyl Radical Catalysis.

An unprecedented VCP-CP (vinylcyclopropane-cyclopentene) rearrangement approach has been established herein by virtue of the pyridine-boronyl radical catalyzed intramolecular ring expansions. This metal-free radical pathway harnesses readily available catalysts and unactivated vinylcyclopropane starting materials, providing an array of cyclopentene derivatives chemoselectively under relatively mild conditions. Mechanistic studies support the idea that the boronyl radical engages in the generation of allylic/ketyl radical species, thus inducing the ring opening of cyclopropanes and the following intramolecular cyclization processes.

Nickel‐Catalyzed Cycloisomerization of 1,5‐Allenynes

AbstractWe report the Ni‐catalyzed cycloisomerization of 1,5‐allenynes. Substrates containing terminal alkynes afford cyclopentene derivatives, whereas internal alkynes lead to the formation of two consecutive C−C bonds to give fused 5–5 bicyclic compounds. The reaction shows a wide scope. Experimental and computational mechanistic studies suggest a Ni(0)−Ni(II) catalytic cycle. The reaction starts with an oxidative cyclometallation followed by a β‐hydrogen elimination. The trans arrangement of alkenyl and hydride ligands is key to allow formation of the second carbocycle.

4+1] Cyclizations to Enantiopure Multifunctional Cyclopentanes from d-Glucose Using Formyl Dianion Synthons

AbstractThe [4+1] cyclization of a sugar-based epoxytosylate with various C1 dianion equivalents provide highly functionalized homochiral cyclopentane derivatives. For these, a follow-up chemistry was developed to provide various cyclopentane building blocks as starting points for natural product syntheses. The [4+1] domino protocol relies on a 1,4-Brook rearrangement, which is essential for generating the second carbanion.

Photoredox‐Enabled Self‐(3+2) Cyclization of Vinyldiazo Reagents: Synthesis of Cyclopentenyl α‐Diazo Compounds

AbstractA photocatalytic self‐(3+2) cycloaddition of vinyldiazo compounds is described, which provides cyclopentene derivatives with conservation of one diazo functional group. Experimental insights and density functional theory indicate that the reaction is triggered by an unusual single electron oxidation of vinyldiazo compounds, while the photolysis for the generation of free carbene species is not involved. The synthetic applications of the resulting cyclopentenyl α‐diazo compounds were demonstrated based on the rich chemistry of the diazo functional group.

Hydrothermal carbonization of food waste digestate solids: Effect of temperature and time on products characteristic and environmental evaluation

Food waste digestate solids (FWDS) is the by-product of anaerobic digestion and it contains high moisture. Hydrothermal carbonization (HTC) has the ability to convert wet bio-waste to hydrochar, which is a potential technology for handling FWDS. This study investigates the effect of reaction temperature and residence time on solid and liquid products from HTC process of FWDS. The solid product was named as hydrochars, and their physicochemical characters were tested and compared. The results showed that temperature had a more significant effect on hydrochar properties, compared to residence time. The higher heating value of hydrochar was 15.46 MJ/kg and the yield was 49%, under reaction conditions of 260 °C and 60 min. It was also found that hydrochar generated at higher temperature had a more stable combustion, higher ignition temperature, higher burnout temperature. For liquid product, the main organic matter are pyridine derivatives, pyrazine derivatives, indole derivatives, cyclopentene derivatives and phenolic compounds. It was also discovered that the increase of temperature can significantly reduce the concentrations of Chemical Oxygen Demand (COD) and Total Organic Carbon (TOC) in liquid product. When reaction temperature increased from 220 ℃ to 260 ℃, the COD decreased from 23,357 mg/L to 19,658 mg/L, TOC decreased from 9827 mg/L to 6352 mg/L, respectively. After HTC under the conditions of 260 °C and 60 min, 67% of nitrogen in solid feedstock e migrated from to liquid product, and N-contained compounds decomposed into ammonia, while phosphorus was mainly remained in the solid phase (>90%), which mainly existed in the form of apatite.

Substituent Effects on Torsional Strain in Cyclopentene Derivatives: A Computational Study.

Density functional theory calculations were used to create a library of ring strain energies (RSEs) for 73 cyclopentene derivatives with potential use as monomers for ring-opening metathesis polymerization (ROMP). An overarching goal was to probe how substituent choice may influence torsional strain, which is the driving force for ROMP and one of the most understudied types of RSEs. Potential trends investigated include substituent location, size, electronegativity, hybridization, and steric bulk. Using traditional and recently developed homodesmotic equations, our results show that the size and substitution (bulk) of the atom directly bonded to the ring have the greatest influence on torsional RSE. A complex interplay between bond length, bond angle, and dihedral angle dictates the relative eclipsed conformations between the substituent and its neighboring hydrogens and was found to be responsible for the notable differences in RSEs. Furthermore, substituents placed on the homoallylic position resulted in higher RSEs than the same substituent placed on the allylic position due to increased eclipsing interactions. Different levels of theory were also assessed, and it was determined that consideration of electron correlation in calculations increased RSEs by ∼2-5 kcal mol-1. Further increasing the level of theory did not significantly change RSEs, indicating that the increased computational cost and time may not be necessary for improved accuracy.

A Computational Study of a Prebiotic Synthesis of Ergosterol, Ergocalciferol & Cholecalciferol (Vitamin D2 and D3)

The magnesium ion metalloporphyrin complex is shown to bind the ligands ethyne (e) and propyne (p) on the metal or nitrogen pyrrole sites as a two-site catalyst in their copolymerization. The order of addition of the monomers is (epep) to form the side-chain. The steroid ring D (pep) is formed first from the propyne adduct bound to the metal site and the nonane adduct bound to the N-site. The optimal orientation of these adducts determines the β-orientation of the 17-substituent. Further addition of three ethyne monomers forms an N-diene cyclopentene derivative able to cyclise to form the steroid ring C (pee) with a trans conformation and a 13-β methyl substituent. Further addition of propyne forms the B-ring (eep), followed by two ethyne to form the A-ring (pee). Reaction with a hydroxyl anion and a proton allows the catalyst to separate. Final hydrogenation renders ergosterol, photolysis leading to ergocalciferol (Vitamin D2). The reactions have been shown to be feasible from the overall enthalpy changes in the ZKE approximation at the HF and MP2 /6-31G* level, and with acceptable activation energies.

Bisabolane sesquiterpene and cyclopentene derivatives from the marine algal-derived endophytic fungus Trichoderma asperellum EN-764

Four undescribed bisabolane sesquiterpenes and one undescribed cyclopentene derivative, together with one undescribed naturally occurring cyclopentenone derivative, were isolated and identified from the culture of the endophytic fungus Trichoderma asperellum EN-764, which was obtained from the marine red alga Palisada papillosa. Their structures were determined by detailed interpretation of NMR and mass spectroscopic data, while the relative and absolute configurations were unambiguously established based on NOESY experiments, modified Mosher's method, X-ray diffraction, and quantum chemical calculations (ECD and DP4+ probability analysis). The antibacterial activities of the isolated compounds were evaluated, and they exhibited inhibitory activity against some aquatic pathogens with MIC values ranging from 4 to 64 μg/mL.

Lewis-Acid-Mediated Intramolecular Cyclization of 4-Aryl-5-allyl-1,2,3-triazoles to Substituted Cyclopentene Derivatives.

4-Aryl-5-allyl-N-fluoroalkyl-1,2,3-triazoles available by a three-component reaction of fluoroalkyl azides, copper acetylides, and allyl halides underwent aluminum halide-mediated transformation to N-(4-halo-2-aryl-cyclopentenyl) imidoyl halides by cyclization of vinyl cation intermediates, followed by halide capture. Utilization of the cyclic products was demonstrated by the synthesis of N-alkenyl amides, amidines, isoquinolines, and tetrazoles or by the subsequent modification of the cyclopentene ring.

Synthesis of Ketonylated Carbocycles via Excited-State Copper-Catalyzed Radical Carbo-Aroylation of Unactivated Alkenes.

Carbocycles are core skeletons in natural and synthetic organic compounds possessing a wide diversity of important biological activities. Herein, we report the development of an excited-state copper-catalyzed radical carbo-aroylation of unactivated alkenes to synthesize ketonylated tetralins, di- and tetrahydrophenanthrenes, and cyclopentane derivatives. The reaction is operationally simple and features mild reaction conditions that tolerate a broad range of functional groups. Preliminary mechanistic studies suggest a reaction pathway beginning with photoexcitation of [CuI-BINAP]2 and followed by a single electron transfer (SET), radical aroylation of unactivated alkenes, radical cyclization, and re-aromatization, affording the desired ketonylated carbocycles.

Cytotoxic Cyclodepsipeptides and Cyclopentane Derivatives from a Plant-Associated Fungus Fusarium sp.

In this work, four new cyclodepsipeptides, fusarihexins C-E (1-3) and enniatin Q (4), four new cyclopentane derivatives, fusarilins A-D (5-8), together with eight known compounds (9-16), were isolated from cultures of the endophytic fungus Fusarium sp. The structures of the isolated compounds were elucidated by analysis of HRMS and NMR spectroscopic data. The absolute configurations were determined using Marfey's method, a modified Mosher's method, single-crystal X-ray diffraction analysis, and ECD analysis. The antitumor activities of the isolated compounds in vitro were evaluated. Cyclodepsipeptides displayed cytotoxicities against the Huh-7, MRMT-1, and HepG-2 cell lines. Compounds 4, 9, 10, and 12 with IC50 values of 1.0-9.1 μM exhibited the most potent cytotoxicities against the three cell lines as compared to the positive control-5-fluorouracil. Compounds 1-3 and 11 exhibited moderate cytotoxic activities (IC50 values of 10.7-20.1 μM).

AlCl3-Catalyzed Cascade Reactions of 1,2,3-Trimethoxybenzene and Adipoyl Chloride: Spectroscopic Investigations and Density Functional Theory Studies.

The reaction of 1,2,3-trimethoxybenzene with adipoyl chloride in the presence of AlCl3 gave two isomeric cyclopentene derivatives, 1,6-bis(2,3,4-trimethoxyphenyl)hexane-1,6-dione, and two demethylation products of aryl methyl ethers. The cyclopentene derivatives including unconjugated or conjugated enones are products formed in a cascade reaction resulting from first the Friedel-Crafts acylation reaction and then aldol condensation. All compounds were optimized by density functional theory calculated using two functional levels, B3LYP and M06-2X, with the 6-311+G(d,p) basis set. The structural properties were established, natural bond orbital analysis of donor-acceptor interactions was carried out, and charges on the atoms and quantum chemical reactivity identifiers were determined to compare the strength of the intramolecular hydrogen bonds formed and their stabilities. To compare the experimental 1H and 13C NMR chemical shifts with the calculated values, NMR chemical shift calculations were carried out using the gauge-invariant atomic orbital method.

Oxidative [2 + 1 + 1 + 1] Annulation of Aldehydes and Methylene Nitriles: Synthesis of Diastereoselective Polysubstituted Cyclopentenes.

Herein, we report a green cascade approach to prepare a variety of diastereoselective polysubstituted cyclopentene derivatives through metal-free oxidative [2 + 1 + 1 + 1] annulation of aldehydes and methylene nitriles. Mechanistic studies demonstrated that the reaction underwent a four-step cascade reaction including air oxidation and Michael addition to obtain the final product. This reaction features readily available starting materials, transition metal-free, eco-friendly operations, gram-scale syntheses, and wide functional group tolerance. The methodology may be useful for the construction of polysubstituted cyano-cyclopentene heterocycles with potential biological activity.

Synthesis of Cyclopentene Derivatives via Electrochemically Induced Intermolecular Selective (3+2) Annulation.

Cyclopentenes are common cores in many natural products, and in bioactive and functional molecules. However, their synthesis remains challenging in terms of harsh conditions, poor selectivity, prefunctionalization of the substrates, over-reliance on volatile activating reagents and the use of noble metals. Herein, we develop an electrochemical mediator-induced intermolecular selective (3+2) annulation of readily available alkenes and alkynes/alkenes, which provides a simple and efficient method for the synthesis of a library of decorated cyclopentenes and cyclopentanes. This protocol features high efficiency, mild reaction conditions, broad substrate scope, good functional group tolerance, and high regioselectivity. Potential applications are demonstrated by gram-scale synthesis as well as the construction of structural diversity and complexity. A preliminary mechanistic investigation was performed, which indicated that an iodine radical and carbon radicals are involved in this transformation.

Synthesis of Cyclopentene Derivatives via Electrochemically Induced Intermolecular Selective (3+2) Annulation

AbstractCyclopentenes are common cores in many natural products, and in bioactive and functional molecules. However, their synthesis remains challenging in terms of harsh conditions, poor selectivity, prefunctionalization of the substrates, over‐reliance on volatile activating reagents and the use of noble metals. Herein, we develop an electrochemical mediator‐induced intermolecular selective (3+2) annulation of readily available alkenes and alkynes/alkenes, which provides a simple and efficient method for the synthesis of a library of decorated cyclopentenes and cyclopentanes. This protocol features high efficiency, mild reaction conditions, broad substrate scope, good functional group tolerance, and high regioselectivity. Potential applications are demonstrated by gram‐scale synthesis as well as the construction of structural diversity and complexity. A preliminary mechanistic investigation was performed, which indicated that an iodine radical and carbon radicals are involved in this transformation.

Chlorinated Cyclopentene Derivatives and Antifungal Activities from Periconia sp. Induced by the One Strain Many Compounds Strategy and Host Plant Culture.

Eleven new chlorinated cyclopentene derivatives, periconsins A-K, and a new diketopiperazine, periconzin, were found from Periconia sp. cultured in three different media by the one strain many compounds strategy. Additionally, the C-1 methyl hydroxylation of chlorinated cyclopentene was found for the first time in the host plant culture. The structures were identified by extensive spectroscopic analyses, electronic circular dichroism (ECD) and 13C NMR calculations, and single-crystal X-ray diffraction. Compounds 3, 5, 7-11, 15, and 17 showed significant antifungal activities against the plant pathogens Periconia sp., Altemaria sp., and Nigrospora oryzae with MICs ≤2 μg/mL. Other compounds had antifungal activities with MICs ≤8 μg/mL. The antifungal structure-activity relationship of these metabolites indicated that the chlorine at C-5 can increase the activity, but the hydroxy group at C-1 lowered the activity.