Ring System Research Articles

Synthesis, structure and Hirshfeld surface analysis of 2-oxo-2H-chromen-4-yl penta-noate.

In the title compound, C14H14O4, the dihedral angle between the coumarin ring system (r.m.s deviation = 0.016 Å) and the penta-noate ring is 36.26 (8)°. A short intra-molecular C-H⋯O contact of 2.40 Å is observed. Hirshfeld surface analysis reveals that 46.1% of the inter-molecular inter-actions are from H⋯H contacts, 28.6% are from H⋯O/O⋯H contacts and 14.7% are from H⋯C/C⋯H.

Gold-Catalyzed Oxidative Rearrangement Strategy to Yield 2-Hydroxycyclohepta-1,3-diene-1-carbonyl Compounds.

A gold-catalyzed oxidative rearrangement of propargyl alcohols, derived from commercially available cyclohex-2-en-1-ones and alkynes, was successfully developed for the efficient synthesis of seven-membered rings. Thorough investigations were conducted to optimize the reaction conditions and evaluate its compatibility with various functional groups. Additionally, this methodology was applied to the formal total synthesis of guanacastepene A, demonstrating its practical utility in complex natural product synthesis. This versatile and efficient approach opens up new possibilities for the construction of diverse seven-membered ring systems, providing valuable building blocks for further exploration in drug discovery and the synthesis of intricate molecules.

Stereoselective polar radical crossover for the functionalization of strained-ring systems

Radical-polar crossover of organoborates is a poweful tool that enables the creation of two C-C bonds simultaneously. Small ring systems have become essential motifs in drug discovery and medicinal chemistry. However, step-economic methods for their selective functionalization remains scarce. Here we present a one-pot strategy that merges a simple preparation of strained organoboron species with the recently popularized polar radical crossover of borate derivatives to stereoselectively access tri-substituted azetidines, cyclobutanes and five-membered carbo- and heterocycles.

Dynamic stereomutation of vinylcyclopropanes with metalloradicals

The ever increasing demands for greater sustainability and lower energy usage in chemical processes call for fundamentally new approaches and reactivity principles. In this context, the pronounced prevalence of odd-oxidation states in less precious metals bears untapped potential for fundamentally distinct reactivity modes via metalloradical catalysis1–3. Contrary to the well-established reactivity paradigm that organic free radicals, upon addition to a vinylcyclopropane, lead to rapid ring opening under strain release—a transformation that serves widely as a mechanistic probe (radical clock)4 for the intermediacy of radicals5—we herein show that a metal-based radical, that is, a Ni(I) metalloradical, triggers reversible cis/trans isomerization instead of opening. The isomerization proceeds under chiral inversion and, depending on the substitution pattern, occurs at room temperature in less than 5 min, requiring solely the addition of the non-precious catalyst. Our combined computational and experimental mechanistic studies support metalloradical catalysis as origin of this profound reactivity, rationalize the observed stereoinversion and reveal key reactivity features of the process, including its reversibility. These insights enabled the iterative thermodynamic enrichment of enantiopure cis/trans mixtures towards a single diastereomer through multiple Ni(I) catalysis rounds and also extensions to divinylcyclopropanes, which constitute strategic motifs in natural product- and total syntheses6. While the trans-isomer usually requires heating at approximately 200 °C to trigger thermal isomerization under racemization to cis-divinylcyclopropane, which then undergoes facile Cope-type rearrangement, the analogous contra-thermodynamic process is herein shown to proceed under Ni(I) metalloradical catalysis under mild conditions without any loss of stereochemical integrity, enabling a mild and stereochemically pure access to seven-membered rings, fused ring systems and spirocycles.

Synthesis of a Library of Terpenoid Alkaloid-Like Compounds Containing Medium-Sized Rings via Reconstruction of the Humulene Skeleton.

The construction of a chemical library based on natural products is a promising method for the synthesis of natural product-like compounds. In this study, we synthesized a terpenoid alkaloid-like compound library based on the humulene skeleton. Our strategy, which enables access to diverse ring systems such as 11-membered monocyclic, oxabicyclic, and medium-sized aza ring-containing scaffolds, involves the introduction of a nitrogen atom, an intermolecular C-O bond formation via Lewis acid-mediated epoxide-opening transannulation, and a ring-reconstruction strategy based on olefin metathesis. A cheminformatics analysis based on their structural and physicochemical properties revealed that the synthesized compounds have high three-dimensionality and high natural product likeness scores but with structural novelty. The usefulness of the terpenoid alkaloid-like compound library for drug discovery and the accessibility to structure-activity relationship studies were validated by performing an assay for osteoclast-specific tartrate-resistant acid phosphatase activity, resulting in the identification of a seed compound for bone-resorptive diseases such as osteoporosis.

UPLC-Q-TOF-MS/MS-Based Targeted Discovery of Chetomin Analogues from Chaetomium cochliodes.

Chetocochliodin M (5) containing a rare cage-ring and chetocochliodin N (6) featuring an unusual piperazine-2,3-dione ring system together with known analogues chetomin (1), chetoseminudin C (2), chetocochliodin I (3), and oidioperazine E (4) were targeted for purification from the fungus Chaetomium cochliodes using a UPLC-Q-TOF-MS/MS approach. The structures of the new compounds were elucidated using HR-ESI-MS, NMR, and ECD spectra. Compounds 1, 3, and 6 exhibited strong cytotoxic activities against A549 and HeLa cancer cell lines.

Polar alignment of a dusty circumbinary disc – I. Dust ring formation

ABSTRACT We investigate the formation of dust traffic jams in polar-aligning circumbinary discs. We use 3D smoothed particle hydrodynamical simulations of both gas and dust to model an initially highly misaligned circumbinary disc around an eccentric binary. As the circumbinary disc evolves to a polar configuration (perpendicular to the binary orbital plane), the difference in the precession between the gas and dust produces dust traffic jams, which become dense dust rings. We find the formation of dust rings exists for different Stokes number, binary eccentricity, and initial disc tilt. Dust rings are only produced while the circumbinary disc is misaligned to the binary orbital plane. When the disc becomes polar aligned, the dust rings are still present and long-lived. Once these dust rings are formed, they drift inward. The drift time-scale depends on the Stokes number. The lower the Stokes number, the faster the dust ring drifts near the inner edge of the disc. The dust rings will have an increased mid-plane dust-to-go ratio, which may be a favourable environment for the steaming instability to operate.

Psathrosterols C–E, highly conjugated ergosterol derivatives from Psathyrella rogueiana with anti-inflammatory and immunosuppressive activity

Three new ergosterols featuring with a highly conjugated ring system, psathrosterols C–E (1–3), have been isolated from the fungus Psathyrella rogueiana. The structures with the absolute configurations were elucidated by means of spectroscopic methods and single crystal X-ray diffraction. Compounds 1–3 exhibit inhibitory activity against NO production with IC50 values ranging from 8.4 to 21.8 μM. Compound 1 inhibits the LPS-induced proliferation of B lymphocyte cells with an IC50 value of 12.3 μM.

Amplified linear and nonlinear chiral sensing assisted by anapole modes in hybrid metasurfaces

The interaction between chiral molecules and circularly polarized light is largely influenced by the local optical chirality density. This interaction prompts substantial demand of the design of nanophotonic platforms capable of enhancing such effects across large and accessible volumes. Such a magnification requires nanostructures that provide strong electric and magnetic field enhancements while preserving the phase relation of circular light. Dielectric nanostructures, particularly those able to support resonances, are ideal candidates for this task due to their capacity for high electric and magnetic field enhancements. On the other hand, efficient third harmonic generation requires strong electric field resonances within dielectric materials, a feature often boosted by incorporating plasmonic materials into hybrid systems. In this work, we numerically propose a coupled silicon disk-gold ring system that can exploit the anapole-induced field confinement to provide a broadband magnified circular dichroism under realistic conditions, reaching values up to a 230-fold enhancement. We also demonstrate that this structure can be employed as an efficient third harmonic generator, which, when integrated with chiral media, enables an 800-fold enhancement in circular dichroism. Furthermore, we show that pulsed illumination at intensities up to 10 GW/cm2 does not induce temperature increments that could potentially damage the samples. These findings suggest that this system can be a promising and versatile approach toward ultrasensitive chiral sensing.

Structurally diverse diterpenoids and phenanthrene derivatives from the roots of Baliospermumsolanifolium

Ten undescribed diterpenoids (1–10) and three undescribed phenanthrene derivatives (11–13), together with seven known compounds, were isolated from the roots of Baliospermum solanifolium. Their structures were determined by a combination of spectroscopic data analysis, electronic circular dichroism calculations and single-crystal X-ray diffraction studies. Compounds 1–7 (baliosperoids A–G) represent the examples of 20-nor-ent-podocarpane class first discovered in nature. In particular, compound 7 possesses a unique 2,3-seco ring system incorporating γ-butanolide moiety. All isolates were assessed for their cytotoxic activities against HT-29, HCT-116, HCT-15, MCF-7, and A549 cell lines as well as their inhibitory effects on lipopolysaccharide-induced NO production in RAW264.7 cells. Compound 1, a 20-nor-ent-podocarpane-type diterpenoid possessing a Δ1,2 double bond, not only exhibited considerable proliferation inhibition against five human cancer cell lines, with IC50 values ranging from 4.13 to 23.45 μM, but also displayed the most potent inhibitory activity on NO production with IC50 value at the nanomolar level (0.63 ± 0.21 μM).

Analysis on the gas-solid variation characteristics and dust spatial distribution in a return micro-cyclone with a tangential inlet

The cyclone separator is widely used for the dedusting process in industry to extend its application scope, a novel return micro-cyclone with a tangential inlet was constructed considering its small and convenient feature. The cyclone was constructed by 3D printing technology, and the experimental system was established. A 3D fluid dynamics (CFD) model was developed with RNG k–ε model and discrete random walk (DRW) model. Discrete Phase Model (DPM) was applied for dust particles of different sizes in the cyclone to investigate the swirl and separation flow. The transient flow field, the tail swinging phenomenon, the outer and inner swirling airflows can be detected vividly. The numerical method predicts the quantity percentage of dust well with the deviations of 0.92 %, 1.15 %, 0.88 %, 0.69 % and 4 % of the experimental data for PM10–20, PM20–30, PM30–40, PM40–50 and PM50–60 when the initial air velocity is 7.3 m/s. There are few dust particles in the exhaust pipe, which are mainly fine particles of PM10 with few particles of PM10–20 and PM20–30 when the initial air velocity is low. The phenomenon of the dust ring at the top region is significant and varies with the air velocity. Dust concentration in different sections can provide further references to optimize the cyclone structure.

Improved Rigidin-Inspired Antiproliferative Agents with Modifications on the 7-Deazahypoxanthine C7/C8 Ring Systems.

To improve their aqueous solubility characteristics, water-solubilizing groups were added to some antiproliferative, rigidin-inspired 7-deazahypoxanthine frameworks after molecular modeling seemed to indicate that structural modifications on the C7 and/or C8 phenyl groups would be beneficial. To this end, two sets of 7-deazahypoxanthines were synthesized by way of a multicomponent reaction approach. It was subsequently determined that their antiproliferative activity against HeLa cells was retained for those derivatives with a glycol ether at the 4'-position of the C8 aryl ring system, while also significantly improving their solubility behavior. The best of these compounds were the equipotent 6-[4-(2-ethoxyethoxy)benzoyl]-2-(pent-4-yn-1-yl)-5-phenyl-1,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 33 and 6-[4-(2-ethoxyethoxy)benzoyl]-5-(3-fluorophenyl)-2-(pent-4-yn-1-yl)-1,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one 59. Similarly to the parent 1, the new derivatives were also potent inhibitors of tubulin assembly. In treated HeLa cells, live cell confocal microscopy demonstrated their impact on microtubulin dynamics and spindle morphology, which is the upstream trigger of mitotic delay and cell death.

Synthesis of HZSM-5@activated carbon for improving aromatic production from catalytic pyrolysis of biomass

HZSM-5 widely used for the catalytic pyrolysis of biomass exhibits the drawbacks of high diffusion resistance and large coke production. To effectively enhance the catalytic efficiency and alleviate the coke deposition, a novel promising catalyst, HZSM-5 coated activated carbon (HZSM-5@AC), was prepared for the first time for in-line upgrading the pyrolysis products of soybean straw. Various catalysts including HZSM-5, activated carbon, and the HZSM-5@AC catalysts with different HZSM-5 to activated carbon mass ratios were characterized. The results showed that the HZSM-5 was successfully coated on the surface of activated carbon and the addition of activated carbon introduced a mesoporous structure and more acidic sites to the catalyst. The catalytic performance on the biomass conversion showed that the catalyst with HZSM-5-to-activated carbon mass ratio of 18:5 (18HZSM-5@5AC) had the highest catalytic efficiency on the conversion of biomass into aromatics with a selectivity of 99.5%, including 75.68% of benzene, toluene, and xylenes (BTX) with a yield of 74.68 mg/g. Moreover, a possible pathway for HZSM-5@AC catalyzed biomass pyrolysis was proposed through analyzing the conversion of model compounds. The catalyst cycling experiments demonstrated the higher stability of HZSM-5@AC than the parent HZSM-5 and activated carbon. TG, FTIR, Raman and SEM showed that the spent HZSM-5@AC was hardly structurally changed with a low coke yield of 0.08%. However, the spent HZSM-5 was partly structurally deactivated by large aromatic ring systems with a coke yield of 3.74%. SEM results also showed that a large amount of polymerized material encapsulated the surface of the spent HZSM-5.

Imidazo[1,2-a]pyridine and Imidazo[1,5-a]pyridine: Electron Donor Groups in the Design of D-π-A Dyes.

This work investigates the electron-donating capabilities of two 10-π electron nitrogen bridgehead bicyclic [5,6]-fused ring systems, imidazo[1,2-a]pyridine and imidazo[1,5-a]pyridine rings. Eight compounds with varying positions of electron-withdrawing moieties (TCF or DCI) coupled to the imidazopyridine ring were synthesized and studied. DCI-containing compounds (Ib-IVb) exhibited a purely dipolar nature with broad absorption bands, weak fluorescence, large Stokes shifts, and strong solvatochromism. In contrast, TCF-containing compounds (Ia-IVa) demonstrated diverse properties. Imidazo[1,2-a]pyridine derivatives Ia and IIa were purely dipolar, while imidazo[1,5-a]pyridine derivatives IIIa and IVa displayed a cyanine-like character with intense absorption and higher quantum yields of emission. The observed gradual red shift in optical properties with changing electron-donor groups (IIb < Ib < IIIb < IVb) and (IIa < Ia < IIIa < IVa) underscores the stronger electron-donor character of imidazo[1,5-a]pyridine compared to that of imidazo[1,2-a]pyridine. Furthermore, crystalline powders of imidazo[1,2-a]pyridine derivatives exhibited fluorescence despite minimal emission in solution. Two compounds (Ib and IVa) were successfully formulated into nanoparticles for potential in vivo imaging applications in zebrafish embryos.

C-H Functionalization-Enabled 11-Step Semisynthesis of (-)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment.

We report an efficient semisynthesis of the cholestane steroidal alkaloid (-)-veragranine A with a 6/6/6/5/6/6 hexacyclic ring system, eight stereocenters, and a unique C12-C23 linkage. Our synthesis features a Schönecker-Baran C-H oxidation at C12, a Suzuki-Miyaura cross-coupling to form the C12-C23 bond, and a hydrogen atom transfer (HAT)-initiated Minisci C-H cyclization to forge the C20-C22 bond with desired stereochemistry at C20. These enabling transformations significantly enhanced the overall synthetic efficiency and delivered (-)-veragranine A in 11 steps and over 200 mg from cheap and readily available dehydroepiandrosterone. In addition, this approach allowed flexible syntheses of novel synthetic analogs for biological evaluations in sensory neurons in vitro and in an in vivo model of arthritic pain, from which two novel lead compounds were identified for further development.

Dearomative Intramolecular meta‐Thermocycloadditions of Benzene Rings via Wheland Intermediates

Dearomative cycloadditions are powerful synthetic transformations utilizing aromatic compounds for cycloaddition reactions. They have been extensively applied to the synthesis of biologically relevant compounds not only because of the complexity generated from simplicity but also the atom‐ and step‐economy. For the most studied yet challenging benzene ring systems, ortho‐ and para‐cycloadditions have been realized both photochemically and thermally, while the meta‐cycloadditions are still limited to the photochemical processes tracing back to the 1960s. Herein, we for the first time realized the thermal cycloadditions of benzene rings with alkenes in a meta fashion via Wheland intermediates. A broad spectrum of readily available C(sp2)‐rich aniline‐tethered enynes were transformed into C(sp3)‐rich 3D complex polycyclic architectures simply by stirring in TFA. Moreover, the reaction could be performed in gram‐scales and the products could be diversely elaborated.

Synthesis and characterization of sulfonamide appended rigid phenyl-based and non-rigid 1,4-benzodioxan-based ring systems and their Pt(II) complexes towards potential therapeutic targets

Two novel non-rigid; 1,4-benzodioxan (bzd) based and rigid; 4-methylbiphenyl (4-Mebip) based di-(2-picolyl)amine derived sulfonamide ligands, and their cis-dichloroplatinum(II) complexes have been synthesized. The ligands; L1: N(SO2)(bzd)dpa and L2: N(SO2)(4-Mebip)dpa were synthesized via N-sulfonylation of di-(2-picolyl)amine in good yield. Their platinum(II) complexes; C1: [PtCl2(N(SO2)(bzd)dpa)], C2: [PtCl2(N(SO2)(4-Mebip)dpa)]·CH3CN were synthesized and characterized by 1H NMR, FTIR, UV–Vis and fluorescence spectroscopies. Structural studies revealed that the L1 and L2 ligands coordinate Pt(II) in a bidentate mode in C1 and C2 complexes, forming an eight-membered chelate ring. Interestingly, L1 possesses two conformations because the dioxan ring exists with a 95:5 occupancy ratio. The L2 ligand crystal undergoes a phase transition to triclinic form with twinning at 90 K whereas, at 150 K, the ligand exists in a monoclinic system; the populations of the two orientations for one pyridine substituent are approximately 78:22. The 1H NMR spectra of both Pt complexes obtained in DMSO‑d6 revealed two doublets (exo-CH2 and endo-CH2) for the magnetically inequivalent methylene protons, in contrast to their uncoordinated ligands, which show a singlet peak for the methylene protons. The NCI-H292 (non-small cell lung cancer cells) and MRC-5 (human normal lung fibroblast cells) were used to examine the in vitro cytotoxic activity of all synthesized compounds. All tested compounds demonstrated notable cytotoxicity against NCI-H292 cells, with the most pronounced cytotoxic effect being displayed by [PtCl2(N(SO2)(4-Mebip)dpa)]·CH3CN (C2). Docking studies strengthen in vivo antiproliferation activity where specific interactions with AKT1, BAX, STK-11, and BCL-2 were explored. Further predictions revealed that the compounds have inhibitory effects on COX-2 and PDE10A proteins.

SOFIA/HAWC+ Far-infrared Polarimetric Large Area CMZ Exploration Survey. II. Detection of a Magnetized Dust Ring in the Galactic Center

We present the detection of a magnetized dust ring (M0.8–0.2) in the central molecular zone (CMZ) of the Galactic center. The results presented in this paper utilize the first data release of the Far-Infrared Polarimetric Large Area CMZ Emission (FIREPLACE) survey (i.e., Paper I of this series). The FIREPLACE survey is a 214 μm polarimetric survey of the Galactic center using the SOFIA/HAWC+ telescope. The M0.8–0.2 ring is a region of gas and dust that has a circular morphology with a central depression. The dust polarization in the M0.8–0.2 ring implies a curved magnetic field that traces the ring-like structure of the cloud. We posit an interpretation in which an expanding shell compresses and concentrates the ambient gas and magnetic field. We argue that this compression results in strengthening of the magnetic field, as we infer from the observations toward the interior of the ring.

Chemical compounds from Osmunda japonica and their NO inhibitory activity

Two new compounds, osmjapterpenoid A (1) and osmunjaponin A (2), along with twenty-six known compounds, were isolated from the roots and rhizomes of Osmunda japonica Thunb. The chemical structures of them were elaborated by extensive spectroscopic means, including 1D, 2D-NMR and HR-ESI-MS. Compound 1 is a diterpenoid derived from cembrane with a novel skeleton of 5/13 dicyclic ring system. The possible biogentic pathway of 1 was deduced. Compounds 3 and 26 exhibited moderate inhibition on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages with IC50 value of 32.09 and 19.81 μM, respectively.

One-pot Synthesis of Condensed Azepines

Abstract: Azepine is a privileged nitrogen-containing ring that has been found to display a wide range of biological activities. Azepine is a valuable skeleton in designing novel compounds in medicinal chemistry due to its interesting chemical and biological properties. The study on the synthesis of this ring system engenders a fascinating area of research owing to its potential to form an active pharmacophore for De Novo exploration. In this study, conventional and domino results were compared to access the diverse set of azepines in high yield. The domino approach has revolutionized the way through which the previously impossible yet significant transformations could be conceptualized, allowing the construction of difficult materials in one step. The aim of the present mini-review is to highlight the importance of the one-pot domino reaction for the synthesis of condensed azepines. This review also presents research on this subject from the past two decades.