Construction Of Ring Research Articles

New construction of a charged dipole black ring by the Harrison transformation

New construction of a charged dipole black ring by the Harrison transformation

[Fe(NCMe)6](BF4)2 is a bifunctional catalyst for styrene aziridination by nitrene transfer and heterocycle expansion by subsequent dipolar insertion

The solvated iron(II) salt [Fe(NCMe)6](BF4)2 (Me = methyl) is shown to be a bifunctional catalyst with respect to aziridination of styrene. The salt serves as an active catalyst for nitrene transfer from PhINTs to styrene to form 2-phenyl-N-tosylaziridine (Ph = phenyl; Ts = tosyl, –S{O}2–p-C6H4Me). The iron(II) salt also acts as a Lewis acid in non-coordinating CH2Cl2 solution, to catalyze heterolytic CN bond cleavage of the aziridine and insertion of dipolarophiles. The 1,3-zwitterionic intermediate is presumably supported by interaction of the metal dication with the anion, and by resonance stabilization of the carbocation. Nucleophilic dipolarophiles then insert to give a five-membered heterocyclic ring. The result is a two-step cycloaddition, formally [2 + 1 + 2], that is typically regiospecific, but not stereospecific. This reaction mechanism was confirmed by conducting a series of one-step, [3 + 2] additions of unsaturated molecules into pre-formed 2-phenyl-N-tosylaziridine, also catalyzed by [Fe(NCMe)6](BF4)2. Relevant substrates include styrenes, carbonyl compounds and alkynes. These yield five-membered heterocylic rings, including pyrrolidines, oxazolidines and dihydropyrroles, respectively. The reaction scope appears limited only by the barrier to formation of the dipolar intermediate, and by the nucleophilicity of the captured dipolarophile. The bifunctionality of an inexpensive, earth-abundant and non-toxic catalyst suggests a general strategy for one-pot construction of heterocyclic rings, as demonstrated specifically for pyrrolidine ring formation.

A Tandem Ring Closure and Nitrobenzene Reduction with Sulfide Provides an Improved Route to an Important Intermediate for the Anti-Tuberculosis Drug Candidate Sutezolid.

Sutezolid is an in-development thiomorpholine derivative of the FDA-approved tuberculosis (TB) treatment linezolid. Current synthetic routes for preparing sutezolid start with thiomorpholine as a key structural building block; unfortunately, this material was identified as a major cost driver for the API, which will limit the potential uptake of this treatment in lower income regions. In this work, an alternative, lower-cost synthetic strategy to a known p-phenylenediamine intermediate to sutezolid has been demonstrated. The key step in this process is the construction of the thiomorpholine ring by a nucleophilic sulfide ring closure on an activated bis(2-hydroxyethyl)-functionalized aniline, which was in turn made by reaction of 3,4-difluoronitrobenzene and diethanolamine. This sulfide treatment has the added benefit of affecting a Zinin reduction of the nitro functional group, which alleviates the need for the transition metal reduction used in previous routes. After optimization, this key reaction was able to provide the desired aniline intermediate in yields between 65 and 80% and, after a standard charcoal treatment, purity of >94%. Initial demonstrations of the full 3-step strategy were successfully conducted on scales up to 100 g with overall yields of 53-68%. This preliminary work will serve as the foundation for a broader low-cost redesign of the sutezolid synthetic process.

Palladium-Catalyzed [5 + 4] Cycloaddition of 4-Vinyl-4-Butyrolactones with N-Tosyl Azadienes: Construction of Nine-Membered Ring.

In this paper, we reported the palladium-catalyzed formal [5 + 4] cycloaddition reactions between 4-vinyl-4-butyrolactones (VBLs) and azadienes. Under mild reaction conditions, a wide range of benzofuran-fused 9-membered heterocyclic compounds had been provided in moderate to excellent yields with exclusive regioselectivities and excellent diastereoselectivities. The practical applicability of the synthesis was demonstrated through scale-up reaction and further transformation.

Construction and finite generation of the strict closure of rings

The construction of Arf rings and strictly closed rings has been studied widely; however, there has been no clear description of the structure of the strict closure R⁎ when R‾ is not a finitely generated R-module. In this paper, we investigate the construction and finite generation of the strict closure of rings. We determine its structure when R is a Cohen-Macaulay semi-local ring of dimension one, with dim⁡RM=1 for every M∈MaxR. Using this, a characterization of the finite generation of the strict closure is given.

Couple-close construction of polycyclic rings from diradicals.

Heteroarenes are ubiquitous motifs in bioactive molecules, conferring favourable physical properties when compared to their arene counterparts1-3. In particular, semisaturated heteroarenes possess attractive solubility properties and a higher fraction of sp3 carbons, which can improve binding affinity and specificity. However, these desirable structures remain rare owing to limitations in current synthetic methods4-6. Indeed, semisaturated heterocycles are laboriously prepared by means of non-modular fit-for-purpose syntheses, which decrease throughput, limit chemical diversity and preclude their inclusion in many hit-to-lead campaigns7-10. Herein, we describe a more intuitive and modular couple-close approach to build semisaturated ring systems from dual radical precursors. This platform merges metallaphotoredox C(sp2)-C(sp3) cross-coupling with intramolecular Minisci-type radical cyclization to fuse abundant heteroaryl halides with simple bifunctional feedstocks, which serve as the diradical synthons, to rapidly assemble a variety of spirocyclic, bridged and substituted saturated ring types that would be extremely difficult to make by conventional methods. The broad availability of the requisite feedstock materials allows sampling of regions of underexplored chemical space. Reagent-controlled radical generation leads to a highly regioselective and stereospecific annulation that can be used for the late-stage functionalization of pharmaceutical scaffolds, replacing lengthy de novo syntheses.

A Versatile, Functional Group-Tolerant, and Bench-Stable Iron Precatalyst for Building Arene and Triazine Rings by [2+2+2] Cycloadditions.

We report an efficient iron-catalyzed cycloaddition procedure leading to the construction of (hetero)aromatic rings by alkyne [2+2+2] cycloisomerization. This method relies on the use of an air-stable (N,N)Fe(II) precursor easily prepared from a commercially available ligand derived from 1,10-phenanthroline, reduced in situ into a catalytically active non-innocent (N,N ⋅- )2 Fe(II) species. This system displays a large scope application, operates under mild conditions and at low catalytic charges (25 cycloadducts formed, up to 1.5 mol% catalyst). Moreover, this method also enables access to 29 cycloadducts by cross-cycloisomerization between 1,6- or 1,7-diynes and alkynes in near-equimolar conditions. 1,3,5-Triazines can also be prepared with this procedure starting from the corresponding cyanamides. Scale-up reactions and post-functionalization of several cycloadducts also show that this [2+2+2] cycloaddition can be used in multistep sequences.

The dynamics of fishing villages along the South Atlantic Coast of North America (ca. 5000–3000 years BP)

We present new chronologies that inform the timing and tempo of shell ring and shell mound construction on the South Atlantic Bight. Our project combines recently acquired dates with legacy radiocarbon dates from over 25 rings and mounds to provide a higher-resolution chronology regarding the occupation and formation of this larger landscape of the earliest fishing villages along the East Coast of the United States. We resolve the ordering and timing of occupation of these rings and mounds through Bayesian statistical modeling. These new models historicize and contextualize these shell rings in ways previously impossible. Specifically, our new chronologies of these villages indicate that the earliest villages were established prior to the invention of pottery. The early period of village establishment evidences isolated village rings, whereas later periods seem to have more villages, but these appear to have been relocated to other areas and/or islands over time. Shell mounds are fewer in number, are spread throughout the time period, and may represent special purpose sites compared to shell-rings. Once villages spread, they quickly adopted new technologies (i.e., pottery) and created new institutions and practiced village relocation, which allowed this way of life to persist for more than a thousand years.

Synthetic Route to Benzostannoles via Al−Li‐dimetal Intermediate and Their Application to Dibenzofulvene Synthesis

AbstractBenzostannoles were synthesized from commercially available and easily accessible substrates. The ring construction proceeds via an Al−Li‐dimetal intermediate generated in situ from 1‐bromo‐2‐(silylethynyl)benzenes. This methodology provided various 2‐silylbenzostannoles in 32% to 97% yields. The benzostannoles obtained were converted into dibenzofulvenes by treatment with 1,2‐dibromobenzenes in the presence of a Pd catalyst. This transformation yielded various types of symmetrical and unsymmetrical dibenzofulvenes, with combination of the benzostannoles and 1,2‐dibromobenzenes.

Enhanced Security in Public Key Cryptography: A Novel Approach Combining Gaussian Graceful Labeling and NTRU Public Key Cryptosystem

This research explores an encryption system that combines the Nth-degree Truncated Polynomial Ring Unit (NTRU) public key cryptosystem with Gaussian Graceful Labeling. This process assigns distinct labels to a graph's vertices, resulting in successive Gaussian integers. The NTRU method offers enhanced security and efficient key exchange. The communication encryption process depends on integers P, a, and b, with P being the largest prime number in the vertex labeling. The original receivers are the vertex labeling with the largest prime number coefficient, while all other receivers receive messages from the sender. A polynomial algebraic mixing system and a clustering principle based on the abecedarian probability proposition are used in NTRU encryption and decryption. The choice of relatively prime integers p and q in NTRU plays a role in the construction of polynomial rings used for encryption and decryption, with specific choices and properties designed to ensure scheme security.

3,4-Diarylisoxazoles-Analogues of Combretastatin A-4: Design, Synthesis, and Biological Evaluation In Vitro and In Vivo.

Focusing on the molecular docking results, a series of 3,4-diarylisoxazoles, analogues of Combretastatin A4, bearing various substituents at the fifth position of the isoxazole ring and pharmacophore groups bioisosteric to methoxy substituent at ring B, were synthesized in good yields and high regioselectivity. Depending on the substituent at C5, three approaches were chosen for the construction of isoxazole ring, including nitrosation of gem-dihalocyclopropanes, nitrile oxide synthesis, and difluoromethoxylation of isoxazolone to afford 5-haloisoxazoles, 5-unsubstituted isoxazoles, and 5-difluoromethoxyisoxazoles, respectively. Isoxazoles 43 and 45 showed selective cytotoxicity and antitubulin inhibition properties in vitro, with pharmacodynamic profiles closely related to that of CA-4. Both of them slow down tumor growth (66-74%) in mouse xenografts and slightly exceed in effectiveness Combretastatin A4-phosphate itself.

Simulation of Wave Propagation in Plasma-Metamaterial Composites Based on Plasma Parameters and Metamaterial Structures

Metamaterial is a left-handed medium used in antenna design to overcome the typical design's larger size and untunable nature. Because of its design with a high permittivity dielectric substrate and some deformation, the wireless sector may be able to solve this difficulty. Metamaterial antennas have a five-fold reduction in size, a higher bandwidth, a wider scanning angle, good beam performance, and electronically controlled targeting. Metamaterials antennas also improve antenna parameters such as frequency generation, gain, and bandwidth. This research aims to suggest the best metamaterials structure for improving antenna performance using plasma as a base. This study used 12 types of plasma with varying plasma frequencies and collision frequencies with four metamaterials structures: 1D-split ring structure, Symmetrical structure, Omega structure, and S structure. Computer Simulation Technology (CST) Studio Suite was used to design and simulate each structure with a sequence of plasma. At frequencies ranging from 1 GHz to 20 GHz, parameters including return loss, gain, radiation pattern, and Voltage Standing Wave Ratio (VSWR) are used to assess an antenna's performance. Due to its electromagnetic qualities, the 1D-split ring construction has a better omnidirectional figure and VSWR value of 1.0039 dB. When all criteria were considered, the best results were obtained when using a 1D-split ring structure of the Plasma 9 (plasma frequency of 3.58528 x1011 rad/s and collision frequency of 1.3349 x109 1/s) produces an efficient return loss, high gain, better VSWR and a better omnidirectional figure among the four structures evaluated.

A Brief Review on Recent Developments in Diels-Alder Reactions.

The [4+2] Diels-Alder cycloaddition has been widely used for the synthesis of six-mem-ber scaffolds. In recent years, there have been significant developments in this area, including the discovery and design of novel dienes and dienophiles with improved reactivity and selectivity. These new building blocks can be used to develop diverse molecular structures with functional group compatibility. Additionally, there is the use of catalytic systems and metal-mediated reactions to enable asymmetric [4+2] cycloadditions, resulting in enantiomerically enriched products. Over-all, recent studies related to [4+2] Diels-Alder cycloaddition using numerous dienes, dienophiles, and catalysts in different reaction conditions have significantly improved the efficiency, selectivity, and versatility of the reaction, making it an increasingly important tool in the synthesis of complex organic molecules as presented in this review. These advancements offer exciting possibilities for the development of new methods and reagents for the construction of six-membered rings and the synthesis of bioactive compounds.

Navigating Excess Complexity: Total Synthesis of Daphenylline.

Retrosynthetic analysis is a framework for designing synthetic routes to complex molecules that generally prioritizes disconnections which reduce molecular complexity. However, strict adherence to this principle can overlook pathways involving highly complex intermediates that can be easily prepared through powerful bond-forming transformations. Herein, we demonstrate this tactic of generating excess complexity, followed by strategic bond-cleavage, as a highly effective approach for the 11-step total synthesis of the Daphniphyllum alkaloid daphenylline. To implement this strategy, we accessed a bicyclo[4.1.0]heptane core through a dearomative Buchner cycloaddition, which enabled construction of the seven-membered ring after C-C bond cleavage. Installation of the synthetically challenging quaternary stereocenter methyl group was achieved through a thia-Paternò-Büchi [2 + 2] photocycloaddition followed by stereospecific thietane reduction, further illustrating how building excess complexity can enable desired synthetic outcomes after strategic bond-breaking events. This strategy leveraging bond cleavage transformations should serve as a complement to traditional bond-forming, complexity-generating synthetic strategies.

A domino reaction strategy for facile and modular construction of synthetically challenging functionalized ortho-fluoroanilines

A new domino approach enables the simultaneous construction of a benzene ring, along with amine and fluorine installation. Resulting ortho-fluoroanilines can be used to synthesize new fluorinated azo dye and antiviral (tetrahydro)quinazolines.

Photoinduced [4 + 2]-cycloaddition reactions of vinyldiazo compounds for the construction of heterocyclic and bicyclic rings.

Highly selective formal [4 + 2]-cycloaddition of vinyldiazoacetates with azoalkenes from α-halohydrazones, as well as with cyclopentadiene and furan, occurs with light irradiation at room temperature, producing highly functionalized heterocyclic and bicyclic compounds in good yields and excellent diastereoseletivity. Under blue light these vinyldiazoacetate reagents selectively form unstable cyclopropenes that undergo intermolecular cycloaddition reactions at a faster rate than their competitive ene dimerization. [4 + 2]-cycloaddition of vinyldiazoacetates with in situ formed azoalkenes produces bicyclo[4.1.0]tetrahydropyridazine derivatives and, together with their cycloaddition using cyclopentadiene and furan that form tricyclic compounds, they occur with high chemoselectivity and diastereocontrol, good functional group tolerance, and excellent scalability. Subsequent transformations portray the synthetic versatility of these structures.

Intramolecular trapping of an iminium salt: rapid construction of quindoline derivatives.

Construction of the pyridine ring is a practical and streamline way to construct a variety of quindoline derivatives. We have developed a novel method for synthesis of quindoline derivatives by means of intramolecular ring-closure reactions of 3-N-methylphenylindoles via an iminium salt intermediate. This practical method has the advantages of a short reaction time, operational simplicity, and nearly quantitative yields; and it can be used for the rapid synthesis of a variety of valuable quindoline derivatives.

Recent advances in the multicomponent synthesis of pyrazoles.

Pyrazole moiety is considered as an important N-heterocycle in pharmaceuticals and many other functional molecules. The utilization of multicomponent reaction is a major tool in the current approaches of pyrazole synthesis. Considering the power and significance of multicomponent pyrazole synthesis, we review herein the latest developments in this field. According to the typical features, the contents are divided into reactions with different NN fragment sources, such as hydrazine, hydrazone, amidine, nitrile, and diazo compounds, in the pyrazole ring construction, covering the works published since 2019 to date.

Concise synthesis of a fused energetic pyrazolotriazine with good performance

A new insensitive high-energy fused pyrazolotriazine was concisely synthesized via fused ring construction and then nitration.

Cox ring of an algebraic stack

We give a proper definition of the multiplicative structure of the following rings: Cox ring of invertible sheaves on a general algebraic stack; Cox ring of rank one reflexive sheaves on a normal and excellent algebraic stack. We show that such Cox rings always exist and establish its (non-)uniqueness in terms of an Ext-group. Moreover, we compare this definition with the classical construction of a Cox ring on a variety. Finally, we give an application to the theory of Mori dream stacks.