Ring Junction Research Articles

Combining molecular modeling approaches to establish the chromatographic enantiomer elution order in the absence of pure enantiomeric standards: A study case with two tetracyclic quinolines

AbstractIn this study, the stereoisomers of two tetracyclic quinolines previously discovered as Pregnane X Receptor ligands were stereodiscriminated with a Chiralcel OD‐H column under normal‐phase conditions. The two compounds are characterized by a C/D cis ring junction and the co‐existence of four diastereoisomers for the presence of a further chiral center at the ring C. A mobile phase made‐up of n‐hexane/2‐PrOH – 99:1 (v/v) allowed to obtain the four peaks of each stereoisomer fully resolved with enantioseparation and enantioresolution factor values up to 2.98 and 11.16, respectively. Due to the lack of pure enantiomeric standards of known stereochemistry, an indirect protocol was successfully applied to define the enantiomeric elution order (EEO) under the identified optimal eluent conditions. This was possible by comparing experimental and theoretical Time‐Dependent Density Functional Theory (TD‐DFT) electronic circular dichroism spectra.In order to confirm the EEOs established through the ab initio calculations, molecular docking simulations were successfully performed with a nonameric model structure of the chiral selector. The results from the docking simulations were in perfect accordance with the results from the TD‐DFT study, thereby confirming the importance of performing multiple methods in the case of indirect attribution of the absolute configuration.

Novel [60]fullerene polymers: Part 1: Synthesis and polymerisation processes through acrylation of N-methyl-o-hydroxy-2-phenyl fulleropyrrolidines and their monomers

This synthesis of functionalized C60 and novel fullerene polymers is described by an extended acrylation functionality via pyrrolidine substitution. The strategy employed required that first C60 was derivatised to mono-fulleropyrrolidine (6,6 ring junctions of C60) was prepared and reacted with acryloyl chloride to obtain the monomer. Addition of azomethine ylide was found to provide a versatile method for derivatization of [60]fullerene. The first step in this study was to prepare low molecular weight hydroxy fulleropyrrolidines by [3 + 2] cycloaddition of azomethine ylide to [60]fullerene through the use of N-methyl glycine in conjunction with benzaldehyde derivatives. The fulleropyrrolidine monomer was made by the reaction of an –OH group of fulleropyrrolidine with acryloyl chloride in the presence of sodium hydroxide in absolute ethanol. The monomers were characterized by UV and FT-IR techniques. Polymerisation was carried out using benzoyl peroxide as a free radical initiator and dimethylformamide was used as a solvent. DMF is an eminently suitable solvent for compounds with a high molecular weight owing to the combined action of its small molecular size. During the polymerisation process it was observed that the monomer and polymer were soluble in DMF. In addition, the higher the dilution of the reactants, the lower the polymerisation rate and the lower the molecular weight of the product.

Concise synthesis of E/F ring spiroethers from tigogenin. Carbaanalogs of steroidal sapogenins and their biological activity

A four-step synthesis of five- and six-membered E/F ring spiroethers from tigogenin has been developed. An efficient strategy that features bis-Grignard reaction of dinorcholanic lactone with appropriate bis(bromomagnesio)alkanes followed by acid-mediated spirocyclization was employed to construct a new class of steroid compounds having E and F ring junction as an oxa-carbacyclic system. The synthesized carbaanalogs interact with liposomes and albumin, and also exhibit antibacterial and antifungal activity, demonstrating their pharmacological potential.

Molecular heterostructure by fusing graphene nanoribbons of different lengths through a pentagon ring junction

Graphene nanoribbons (GNRs) have attracted great research interest because of their widely tunable and unique electronic properties. The required atomic precision of GNRs can be realized via on-surface synthesis method. In this work, through a surface assisted reaction we have longitudinally fused the pyrene-based graphene nanoribbons (pGNR) of different lengths by a pentagon ring junction, and built a molecular junction structure on Au (111). The electronic properties of the structure are studied by scanning tunneling spectroscopy (STS) combined with tight binding (TB) calculations. The pentagon ring junction shows a weak electronic coupling effect on graphene nanoribbons, which makes the electronic properties of the two different graphene nanoribbons connected by a pentagon ring junction analogous to type I semiconductor heterojunctions.

Isosteroidal alkaloids of Fritillaria taipaiensis and their implication to Alzheimer's disease: Isolation, structural elucidation and biological activity

Four undescribed and five known isosteroidal alkaloids were isolated from the bulbs of Fritillaria taipaiensis and their structures were elucidated on the basis of HR-ESI-MS, 1D and 2D NMR spectroscopic data analyses. The undescribed compounds were designated taipainines A−D. Of these, taipainine D presented a unique structure having the D/E trans (H-13α/H-17β) and E/F cis (β-axial lone pair of the N atom/H-22β) ring junctions. Possible biosynthetic pathway to taipainine D is proposed. Four compounds showed significant BChE inhibitory activities similar or better than the positive control galantamine. In addition, the preliminary structure−activity relationships (SARs) of these isosteroidal alkaloids were also investigated.

Synthesis of Novel C/D Ring Modified Bile Acids.

Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure–activity relationships and define compounds that activate these receptors selectively. Towards this, access to large quantities of a chenodeoxycholic acid derivative bearing a C-12 methyl and a C-13 to C-14 double bond provided an interesting scaffold to investigate the chemical manipulation of the C/D ring junction in bile acids. The reactivity of this alkene substrate with various zinc carbenoid species showed that those generated using the Furukawa methodology achieved selective α-cyclopropanation, whereas those generated using the Shi methodology reacted in an unexpected manner giving rise to a rearranged skeleton whereby the C ring has undergone contraction to form a novel spiro–furan ring system. Further derivatization of the cyclopropanated steroid included O-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation.

(±)‐cis‐4a‐alkyl‐1,3,4,4a,9,9a‐hexahydro‐2H‐carbazol‐2‐ones by domino nitro reduction‐aza‐Michael addition to enones

AbstractA domino nitro reduction‐aza‐Michael addition sequence has been investigated for α,β‐unsaturated ketones and compared with the analogous reaction for conjugated esters. As expected, six‐membered ring closures of ketones did not proceed as well as for esters (<60% vs. >85%) due to the greater inherent reactivity of the ketones. This problem was minimized by performing the cyclization at lower temperature for a shorter time. The process has been extended to a synthesis of (±)‐cis‐4a‐alkyl‐1,3,4,4a,9,9a‐hexahydro‐2H‐carbazol‐2‐ones with good yields (65%–86%). While the rigidity of the system and closure of the smaller five‐membered ring created some strain in the products, yields were acceptable. The cis ring junction resulted from axial attack to give a more stable chair‐like enol that tautomerized to the target heterocycle.

Compact wideband five‐port reflectometer based on symmetrical waveguide ring junction for synthetic microwave imaging applications

SummaryA compact and symmetrical five‐port reflectometer (FPR) for microwave imaging application is introduced in this paper. The proposed FPR shows a wide operational impedance matching bandwidth in the frequency span of 1.55–5.31 GHz (about 109.6%). It consists of three layers with a compact size of 42.4 × 42.4 × 3.2 mm3 and comprises five symmetric branch lines which were designed and optimized as a star junction topology and placed at the middle layer to realize an equivalent value of 70 dB for reflection coefficients at a center operating frequency of 2 GHz. Moreover, the measured results indicate that the FPR prototype has realized accuracies of approximately ± 120° in phase, 0.04 and 0.5 magnitudes of reflections and transmission coefficients, respectively, which are relative in parallel to the simulated and theoretical results. The proposed FPR proves higher efficacious capabilities to be used in microwave imaging for biomedical application systems.

Flow dearomatization of electron-poor 3-fluoromethylthioindoles by 1,3-dipolar cycloaddition

Indoles substituted by electron-depleted thio groups at positions 1 and 3 react as C2 = C3 dipolarophiles with an electron-rich azomethine ylide dipole under flow conditions. The dearomatizing (3 + 2) cycloadditions readily occur to afford the corresponding fluorinated 3D-pyrrolidinoindolines bearing a tetrasusbtituted carbon centre at the ring junction.

Novel Machaeriol Analogues as Modulators of Cannabinoid Receptors: Structure-Activity Relationships of (+)-Hexahydrocannabinoids and Their Isoform Selectivities.

Machaeriols are an important class of compounds that structurally resemble tetrahydrocannabinol (Δ9-THC), with the major differences being inverted stereochemistry at the ring junction as [6aR, 10aR] and an additional stereocenter at the C9 position of the A-ring due to saturation. A previous study reported that machaeriols did not show any cannabinoid receptor activity, even though these hexahydrodibenzopyran analogues mimic a privileged (+)-tetrahydrocannabinoid scaffold. To unravel structural requisites for modulation of cannabinoid receptors, a simple late-stage divergent approach was undertaken to functionalize the machaeriol scaffold using the Suzuki coupling reaction. Fourteen hexahydro analogues were synthesized and screened against both cannabinoid receptor isoforms, CB1 and CB2. Interestingly, many of the analogues showed a significant binding affinity for both receptors; however, two analogues, 11H and 11J, were identified as possessing CB2 receptor-selective functional activity in the GTPγS assay; they were found to be micromolar-range agonists, with EC50 values of 5.7 and 16 μM, respectively. Furthermore, molecular dynamics simulations between the CB2 receptor and two novel analogues resulted in unique interaction profiles by tightly occupying the active ligand-binding domain of the CB2 receptor and maintaining stable interactions with the critical residues Phe94, Phe281, and Ser285. For the first time, with the aid of structure–activity relationships of (+)-hexahydrocannabinoids, CB2 selective agonists were identified with late-stage diversification using palladium-mediated C–C bond formation. By simply switching to (R)-citronellal as a chiral precursor, enantiomerically pure (−)-hexahydrocannabinoids with better CB1/CB2 receptor isoform selectivity can be obtained using the current synthetic approach.

Anthracene and pyrene ruthenacarboranes

Dehalogenation of the anion [3,3-(PPh3)2-3-Cl-closo-3,1,2-RuC2B9H11]− in the presence of toluene, anthracene and pyrene affords the new ruthenacarborane species [3-(C6H5Me)-closo-3,1,2-RuC2B9H11] (1), [3-C14H10-closo-3,1,2-RuC2B9H11] (2) and [3-C16H10-closo-3,1,2-RuC2B9H11] (3), respectively. Compounds 2 and 3 are the first examples of anthracene and pyrene metallacarboranes. In 2 and 3 the orientation of the polycyclic aromatic hydrocarbon (PAH) with respect to the metallacarborane cage is controlled by the relatively weak trans influences of the cage C atoms and the ligating ring junction C atoms of the PAH compared to the relatively strong trans influences of the facial B atoms of the carborane and the ligating non-junction atoms of the PAH. Thus is demonstrated a pronounced structural anthracene effect and structural pyrene effect, to complement established structural indenyl and structural naphthalene effects in metallacarborane chemistry.

Meroterpenoids from the leaves of Psidium guajava (guava) cultivated in Korea using MS/MS-based molecular networking

MS/MS-based molecular networking showed differences in the chemical profiles, especially the terpenoid-coupled-phloroglucinol clusters, of Psidium guajava grown in Jeju Island of South Korea (“Jejuguava”), Vietnam and China. A chemical investigation of the 95% EtOH extract of Jejuguava leaves revealed meroterpenoids characterized by a dihydropyran ring junction between an acylphloroglucinol structure and terpenoid, and named jejuguajavones A–J (1–10). Compounds (±)-8–(±)-10 are racemic mixtures that were separated using a chiral HPLC column. The chemical structures of all the isolated compounds (1–10) were determined by analyzing the spectroscopic data and performing electronic circular dichroism calculations. Among the isolates, compounds 1–4 exhibit inhibitory activity against the protein tyrosine phosphatase 1B (PTP1B) enzyme, and this result was confirmed by molecular docking simulations.

Quantum interference and the time-dependent radiation of nanojunctions

Using the recently developed time-dependent Landauer-B\"uttiker formalism and Jefimenko's retarded solutions to the Maxwell equations, we show how to compute the time-dependent electromagnetic field produced by the charge and current densities in nanojunctions out of equilibrium. We then apply this formalism to a benzene ring junction, and show that geometry-dependent quantum interference effects can be used to control the magnetic field in the vicinity of the molecule. Then, treating the molecular junction as a quantum emitter, we demonstrate clear signatures of the local molecular geometry in the non-local radiated power.

Dynamically Driven Emergence in a Nanomagnetic System

AbstractEmergent behaviors occur when simple interactions between a system's constituent elements produce properties that the individual elements do not exhibit in isolation. This article reports tunable emergent behaviors observed in domain wall (DW) populations of arrays of interconnected magnetic ring‐shaped nanowires under an applied rotating magnetic field. DWs interact stochastically at ring junctions to create mechanisms of DW population loss and gain. These combine to give a dynamic, field‐dependent equilibrium DW population that is a robust and emergent property of the array, despite highly varied local magnetic configurations. The magnetic ring arrays’ properties (e.g., non‐linear behavior, “fading memory” to changes in field, fabrication repeatability, and scalability) suggest they are an interesting candidate system for realizing reservoir computing (RC), a form of neuromorphic computing, in hardware. By way of example, simulations of ring arrays performing RC approaches 100% success in classifying spoken digits for single speakers.

Gibbosolide A, a highly functionalized 20-membered macrolide with a terminal cis-fused 2-methylhexahydro-2H-furo[3,2-b]pyran motif: insights into late-stage cyclization of marine macrolides

The planar structure and absolute configuration of a sailboat-shaped marine macrolide, featuring twelve carbon stereocenters and a cis-fused ether ring juncture, were unambiguously established by a combined approach of chemistry and spectroscopy.

Understanding the Mechanism and Selectivities of the Reaction of Meta-Chloroperbenzoic Acid and Dibromocarbene with β-Himachalene: A DFT Study

This study was performed to understand the site selectivity in the reaction between β-himachalene and meta-chloroperbenzoic acid (m-CPBA) in the first step followed by the addition of dibromocarbene (CBr2) to the main monoepoxidation product Pα formed in the first reaction. Calculations were performed using the Becke three-parameter hybrid exchange functional and the Lee–Yang–Parr correlation functional (B3LYP) with the 6-311 + G (d, p) basis set. Transition states were located by QST2, and their highlighting was validated by the existence of only one imaginary frequency in the Hessian matrix. The action of m-CPBA on β-himachalene was analyzed on the two double bonds of β-himachalene whose theoretical calculations show that the attack affects the most substituted double bond on α side containing hydrogen of ring junction. The obtained Pα product thereafter treated with dibromocarbene leads via an exothermic reaction to the six-membered ring double bond position of α-monoepoxide. The major products Pαα are kinetically and thermodynamically favored with a high stereoselectivity in perfect correlation with the experimental observations.

Theoretical study on the Al-doped biphenylene nanosheets as NO sensors

Based on density functional theory calculations, we have studied the effect of Al doping on the electronic structure and gas-sensing properties of biphenylene (BP) nanosheets. We considered all possible NO adsorption centers on BP and Al-BP sheets. If a sp2 carbon atom located at the 4-, 6-, and 8-membered rings junction of the BP nanostructure is replaced by an Al atom, a NO molecule is adsorbed horizontally on the doped site with ΔG of −47.06 kcal mol−1. The HOMO-LUMO energy gap (Eg) decreases upon Al doping, which results in reduction of resistivity and therefore, Al-BP1 can detect the NO molecule.

De Novo Synthesis of the DEF-Ring Stereotriad Core of the Veratrum Alkaloids.

The synthesis of the stereotriad core in the eastern portion of the Veratrum alkaloids jervine (1), cyclopamine (2), and veratramine (3) is reported. Starting from a known β-methyltyrosine derivative (8), the route utilizes a diastereoselective substrate-controlled 1,2-reduction to establish the stereochemistry of the vicinal amino alcohol motif embedded within the targets. Oxidative dearomatization is demonstrated to be a viable approach for the synthesis of the spirocyclic DE ring junction found in jervine and cyclopamine.

A compact energy harvesting multiband rectenna based on metamaterial complementary split ring resonator antenna and modified hybrid junction ring rectifier

This article presents an improved wireless energy harvesting multiband rectifying antenna. The proposed design is based on an original optimized bidirectional complimentary split ring resonator (CSRR) metamaterial multiband antenna and a modified hybrid junction ring rectifier with four rectifying branches. It harvests the ambient radiofrequency radiations at GSM, 1.8 GHz; UMTS, 2.1 GHz; WiFi, 2.45 GHz; and 4G-2.6 GHz GSM bands. The created prototypes are printed on a 1.57-mm-thickness FR4 substrate and achieve the needed dimensional optimization in both antenna and rectifier. The CSRR antenna accomplished a maximum harvesting realized gain of 2.41, 2.26, 1.58, and 2.69 dB on the aforementioned frequency bands, respectively, 63.75% of antenna size reduction, and 23.62% rectifier size reduction regarding the conventional designs. The hybrid ring junction is used to independently match the subrectifiers at each frequency band. The realized rectenna has been accurately tested in both controlled and outdoor environments, achieving a 67.6% peak efficiency at 1.8 GHz frequency band for an input power level of 10 dBm. It powered up a digital batteryless watch in the outdoor experiment.

Amphilectene Diterpene Isonitriles and Formamido Derivatives from the Hainan Nudibranch Phyllidia Coelestis.

Terpene content of two distinct collections of the nudibranch Phyllidia coelestis from the South China Sea has been chemically analyzed. A series of amphilectene diterpenes, most likely of dietary origin, with isocyano and formamido functionalities have been isolated from both collections and spectroscopically characterized by an exhaustive nuclear magnetic resonance (NMR) analysis. Interestingly, the structural architecture of compounds 5–7 and 9 with both 8,13-cis and 12,13-cis ring junctions is unprecedented in the amphilectene skeleton. Metabolite 3, which was the most abundant in the nudibranch’s mantle, has been shown to deter feeding by a generalist predator, supporting its involvement in chemical defense.