Generation of multimillion chemical space based on the parallel Groebke-Blackburn-Bienaymé reaction.

Parallel Groebke-Blackburn-Bienaymé reaction was evaluated as a source of multimillion chemically accessible chemical space. Two most popular classical protocols involving the use of Sc(OTf)3 and TsOH as the catalysts were tested on a broad substrate scope, and prevalence of the first method was clearly demonstrated. Furthermore, the scope and limitations of the procedure were established. A model 790-member library was obtained with 85% synthesis success rate. These results were used to generate a 271-Mln. readily accessible (REAL) heterocyclic chemical space mostly containing unique chemotypes, which was confirmed by comparative analysis with commercially available compound collections. Meanwhile, this chemical space contained 432 compounds that already showed biological activity according to the ChEMBL database.

Enhanced Energetic Performance via the Combination of Furoxan and Oxa-[5,5]bicyclic Structures.

Three new compounds based on the combination of furoxan (1,2,5-oxadiazole N-oxide) and oxa-[5,5]bicyclic ring were synthesized. Among them, the nitro compound showed satisfactory detonation properties (Dv, 8565 m s-1; P, 31.9 GPa), which is comparable to the performance of RDX (a classic high-energy secondary explosive). Additionally, the introduction of the N-oxide moiety and oxidation of the amino group more effectively improved the oxygen balance and density (d, 1.81 g cm-3; OB%, +2.8%) of the compounds compared to furazan analogues. Combined with good density and oxygen balance as well as moderate sensitivity, this type of furoxan and oxa-[5,5]bicyclic structure will open up a platform for the synthesis and design of new high-energy materials.

Controlling of Photophysical Behavior of Rhenium(I) Complexes with 2,6-Di(thiazol-2-yl)pyridine-Based Ligands by Pendant π-Conjugated Aryl Groups.

The structure-property correlations and control of electronic excited states in transition metal complexes (TMCs) are of high significance for TMC-based functional material development. Within these studies, a series of Re(I) carbonyl complexes with aryl-substituted 2,6-di(thiazol-2-yl)pyridines (Arn-dtpy) was synthesized, and their ground- and excited-state properties were investigated. A number of condensed aromatic rings, which function as the linking mode of the aryl substituent, play a fundamental role in controlling photophysics of the resulting [ReCl(CO)3(Arn-dtpy-κ2N)]. Photoexcitation of [ReCl(CO)3(Arn-dtpy-κ2N)] with 1-naphthyl-, 2-naphthyl-, 9-phenanthrenyl leads to the population of 3MLCT. The lowest triplet state of Re(I) chromophores bearing 9-anthryl, 2-anthryl, 1-pyrenyl groups is ligand localized. The rhenium(I) complex with appended 1-pyrenyl group features long-lived room temperature emission attributed to the equilibrium between 3MLCT and 3IL/3ILCT. The excited-state dynamics in complexes [ReCl(CO)3(9-anthryl-dtpy-κ2N)] and [ReCl(CO)3(2-anthryl-dtpy-κ2N)] is strongly dependent on the electronic coupling between anthracene and {ReCl(CO)3(dtpy-κ2N)}. Less steric hindrance between the chromophores in [ReCl(CO)3(2-anthryl-dtpy-κ2N)] is responsible for the faster formation of 3IL/3ILCT and larger contribution of 3ILCTanthracene→dtpy in relation to the isomeric complex [ReCl(CO)3(9-anthryl-dtpy-κ2N)]. In agreement with stronger electronic communication between the aryl and Re(I) coordination centre, [ReCl(CO)3(2-anthryl-dtpy-κ2N)] displays room-temperature emission contributed to by 3MLCT and 3ILanthracene/3ILCTanthracene→dtpy phosphorescence. The latter presents rarely observed phenomena in luminescent metal complexes.

Selenocyclization by Formation of Carbon-nitrogen Bonds.

Selenium promoted-cyclization of unsaturated substrates containing internal nitrogen nucleophiles, such as different amines and amides, including the examples of its application in the synthesis of more complex polycyclic compounds is reviewed. Selenocyclization reactions of some more specific polyfunctional substrates, like Biginelli hybrids and hydantoins, are also covered.

Deconstructive Asymmetric Total Synthesis of Morphine-Family Alkaloid (-)-Thebainone†A.

Herein, we describe the development of a deconstructive strategy for the first asymmetric synthesis of (-)-thebainone A, capitalizing on an enantioselective C-C bond activation and a C-O bond cleavage reaction. The rhodium-catalyzed asymmetric "cut-and-sew" transformation between sterically hindered trisubstituted alkenes and benzocyclobutenones allowed efficient construction of the fused A/B/C rings and the quaternary center of the natural product. The newly optimized conditions show broad substrate scope and excellent enantioselectivity (up to 99.5:0.5 er). Taking advantage of boron-mediated ether bond cleavage, we completed the synthesis of the morphine alkaloid (-)-thebainone A by two complementary routes.

An Electron Acceptor Analogue for Lowering Trap Density in Organic Solar Cells.

Typical organic semiconductor materials exhibit a high trap density of states, ranging from 1016 to 1018  cm-3 , which is one of the important factors in limiting the improvement of power conversion efficiencies (PCEs) of organic solar cells (OSCs). In order to reduce the trap density within OSCs, a new strategy to design and synthesize an electron acceptor analogue, BTPR, is developed, which is introduced into OSCs as a third component to enhance the molecular packing order of electron acceptor with and without blending a polymer donor. Finally, the as-cast ternary OSC devices employing BTPR show a notable PCE of 17.8%, with a low trap density (1015  cm-3 ) and a low energy loss (0.217 eV) caused by non-radiative recombination. This PCE is among the highest values for single-junction OSCs. The trap density of OSCs with the BTPR additives, as low as 1015  cm-3 , is comparable to and even lower than those of several typical high-performance inorganic/hybrid counterparts, like 1016  cm-3 for amorphous silicon, 1016  cm-3 for metal oxides, and 1014 to 1015  cm-3 for halide perovskite thin film, and makes it promising for OSCs to obtain a PCE of up to 20%.

Antiviral Activities of Pyridine Fused and Pyridine Containing Heterocycles, A Review (from 2000 to 2020).

Heterocyclic compounds play a critical role in medicinal chemistry, and many available drugs contain heterocyclic rings. A six-membered heterocyclic compound, pyridine, showed various applications, including being an important solvent, reagent, and precursor in agrochemicals and pharmaceuticals. Due to the increase in drug resistance, there is an apparent medical need to develop new antiviral agents. Various derivatives of pyridine scaffold display broad biological activities such as anti-microbial, antiviral, antioxidant, anti-diabetic, anti-cancer, anti-malarial, analgesic, and antiinflammatory activities. Furthermore, they display psychopharmacological, antagonistic, anti-amoebic agents, and anti-thrombic activities. Due to the high importance of pyridine derivatives, in the present review, we tried to collect and classify many pyridine derivatives based on their structures from 2000 to 2020. Pyridine derivatives were classified into two general categories, including pyridine containing heterocycles and pyridine fused rings. The structure-activity relationship (SAR) and the action mechanism of derivatives were also investigated. According to the recent studies, these derivatives exhibited good antiviral activity against different types of viruses such as the human immunodeficiency viruses (HIV), the hepatitis C virus (HCV), the hepatitis B virus (HBV), respiratory syncytial virus (RSV), and cytomegalovirus (CMV). These derivatives inhibited viral application with different action mechanism such as RT inhibition, polymerase inhibition, inhibition of RNase H activity, inhibition of maturation, inhibition of the viral thymidine kinase, AAK1 (Adaptor-Associated Kinase 1) inhibition, GAK (Cyclin G-associated kinase) inhibition, inhibition of post-integrational event, inhibition of HDAC6, CCR5 antagonistic activity, DNA and RNA replication inhibition, gene expression inhibition, cellular NF-jB signaling pathway and neuraminidase (NA) inhibition, protein synthesis inhibition, and generally inhibition of viral replication cycle. This paper summarized the past and present results about the discovery of novel lead compounds with good antiviral activity. Studies exhibited that almost all of the evaluations were performed by way of in vitro testing. It is necessary to investigate in vivo and clinical testing for better evaluations in the future. We believe that pyridine derivatives can be used as promising antiviral agents and more broad investigations in this field need to be performed.

Synthesis of Polybenzoacenes: Annulative Dimerization of Phenylene Triflate by Twofold C-H Activation.

Polycyclic aromatic hydrocarbons (PAHs) represent an emerging class of π-conjugated molecules in the area of optoelectronic devices and materials. Unprecedented synthetic routes to various PAHs from simple phenol derivatives by a palladium-catalyzed annulative dimerization of phenylene triflate through twofold inter- and intramolecular C-H activation have been established. The initially formed partially fused PAHs can be smoothly transformed into a variety of fully fused PAHs by the Scholl reaction. Furthermore, the reactions of phenanthrene-substituted aryl triflates proceeded regioselectively. The findings inspired the development of a rapid and efficient synthesis of polybenzoacene derivatives. This study not only allows transformation of phenyl triflates, but also discloses a new retrosynthetic strategy towards PAHs, especially polybenzoacenes.

12-Ethyl-6a,10a-di-hydro-5H-6-oxachrysene.

In the title compound, C19H16O, the pyran ring is in a half-chair conformation. The essentially planar naphthalene ring system (r.m.s. deviation = 0.020 Å) forms a dihedral angle of 14.37 (5)° with the fused benzene ring. In the crystal, pairs of mol-ecules are connected into inversion dimers by weak C-H⋯O hydrogen bonds to generate R 2 2(6) loops.

Design, synthesis and bioevaluation of tricyclic fused ring system as dual binding site acetylcholinesterase inhibitors.

Due to recently discovered non-classical acetylcholinesterase (AChE) function, dual binding-site AChE inhibitors have acquired a paramount attention of drug designing researchers. The unique structural arrangements of AChE peripheral anionic site (PAS) and catalytic site (CAS) joined by a narrow gorge, prompted us to design the inhibitors that can interact with dual binding sites of AChE. Eighteen homo- and heterodimers of desloratadine and carbazole (already available tricyclic building blocks) were synthesized and tested for their inhibition potential against electric eel acetylcholinesterase (eeAChE) and equine serum butyrylcholinesterase (eqBChE). We identified a six-carbon tether heterodimer of desloratadine and indanedione based tricyclic dihydropyrimidine (4c) as potent and selective inhibitor of eeAChE with IC50 value of 0.09 ±â€¯0.003 µM and 1.04 ±â€¯0.08 µM (for eqBChE) with selectivity index of 11.1. Binding pose analysis of potent inhibitors suggest that tricyclic ring is well accommodated into the AChE active site through hydrophobic interactions with Trp84 and Trp279. The indanone ring of most active heterodimer 4b is stabilized into the bottom of the gorge and forms hydrogen bonding interactions with the important catalytic triad residue Ser200.

The Chemistry and Properties of Energetic Materials Bearing [1,2,4]Triazolo[4,3-b][1,2,4,5]tetrazine Fused Rings.

Treatment of heterocyclic amines featuring fused rings of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine with fuming HNO3 /P2 O5 leads to six fully characterized explosives through multiple nitration and reduction or oxidation mechanism. Thus, 4-nitro-N-(3-nitro[1,2,4]triazolo[4,3-b][1,2,4,5]tetrazin-6-yl)-1,2,5-oxadiazol-3-amine (3 b, TTDNF) showed high performance (D=9180 m s-1 , P=36.7 GPa) and low impact sensitivity (IS>40 J) while N-([1,2,4]triazolo[4,3-b][1,2,4,5]tetrazin-6-yl)-3-nitro-1,2,4-oxadiazol-5-amine (4 a, TTNOA) exhibited a potential cast explosive component with low melting point at 88.2 °C and high onset decomposition temperature at 226.2 °C.

Phthalorubines: Fused-Ring Compounds Synthesized from Phthalonitrile.

A series of dibenzo[a,f][1,3,5]triazino[2,1,6-cd] pyrrolizine compounds have been synthesized from phthalonitriles by a facile intramolecular cyclization process using "half-phthalocyanine" precursors, and they were characterized by X-ray crystallography, 1 H NMR spectroscopy, UV/Vis, and theoretical calculations. These compounds have spectroscopic profiles similar to phthalocyanines and porphyrins, although their inner-core structures and coordination types are totally different. They can be regarded as a new class of aromatic fused-ring compounds. The low-energy absorption of these new fused-ring compounds are located at around 600 nm. Such a low-energy π-π* transition is scarce in aromatic compounds having a similar molecular size. According to the nomenclature of phthalocyanines, these types of compounds have been named phthalorubines (Prs).

An Imide-Based Pentacyclic Building Block for n-Type Organic Semiconductors.

A new electron-deficient unit with a fused 5-membered heterocyclic ring was developed by replacing a cyclopenta-1,3-diene from electron-rich donor indacenodithiophene (IDT) with a cyclohepta-4,6-diene-1,3-diimde unit. The imide bridge endows dithienylbenzenebisimide (BBI) with a fixed planar configuration and low energy levels for both the highest occupied molecular orbital (HOMO; -6.24 eV) and the lowest unoccupied molecular orbit (LUMO; -2.57 eV). Organic field-effect transistors (OFETs) based on BBI polymers exhibit electron mobility up to 0.34 cm2 V-1 s-1 , which indicates that the BBI is a promising n-type building block for optoelectronics.

Traceless Solid-Phase Synthesis of Fused Chiral Macrocycles via Conformational Constraint-Assisted Cyclic Iminium Formation.

Natural products comprising chiral molecular scaffolds containing fused medium-sized cycles and macrocycles represent an important and relevant pharmacological target for the discovery and development of new drugs. Here, we describe traceless solid-phase synthesis of acyclic intermediates amenable to cyclization to medium (11) and large (12) fused rings. The key aspect of the synthetic strategy is incorporation of a specific conformation constraint that facilitates cyclization in favor of 11- and 12-membered rings rather than possible 7-membered ones. The role of constraints in preorganization required for cyclization is supported by computational analysis. The synthesis involves cyclic N-sulfonyliminium-nucleophilic addition chemistry as the key ring-forming reaction and proceeds with complete stereocontrol of the newly formed stereogenic center. We document the scope and limitations of this strategy in the synthesis of 11+5, 11+6, 11+7, and 12+6 fused rings representing molecular scaffolds with 3D architecture that mimic complex natural products.

Investigations into the construction of the penta-substituted ring C of Neosurugatoxin - a crystallographic study.

The crystal structures of three cyclo-penta-[c]furans with various substituents at the 4-, 5- and 6-positions of the ring system are reported, namely, (±)-(3aR,4S,5S,6aS)-4-methyl-5-phenyl-hexa-hydro-1H-cyclo-penta-[c]furan-4,5-diol, C14H18O3, (I), (±)-(3aR,4S,5S,6aS)-4-benz-yloxy-4-methyl-5-phenyl-hexa-hydro-1H-cyclo-penta-[c]furan-5-ol, C21H24O3, (II), and (±)-(1aR,1bS,4aR,5S,5aR)-5-benz-yloxy-5-methyl-5a-phenyl-hexa-hydro-2H-oxireno[2',3':3,4]cyclopenta-[1,2-c]furan, C21H22O3, (III). The dominant inter-action in (I) and (II) is an O-H⋯O hydrogen bond across the bicyclic 5,5-ring system between the non-functionalized hy-droxy group and the tetra-hydro-furan O atom, which appears to influence the envelope conformations of the fused five-membered rings, whereas in (III), the rings have different conformations. A weak intra-molecular C-H⋯O inter-action appears to influence the degree of tilt of the phenyl ring attached to the 5-position and is different in (I) compared to (II) and (III).

Rigidifying Nonplanar Perylene Diimides by Ring Fusion Toward Geometry-Tunable Acceptors for High-Performance Fullerene-Free Solar Cells.

Rigid fused perylene diimide (PDI) dimers bridged with heterocycles exhibit superior photovoltaic performance compared to their unfused semiflexible analogues. Changing the chalcogen atoms in the aromatic bridges gradually increases the twist angles between the two PDI planes, leading to a varied morphology in which the one bridged by thiophene achieves a balance and shows the best efficiency of 6.72%.

Crystal structure of (1R,3S,8R,11R)-11-acetyl-3,7,7-trimethyl-10-oxatri-cyclo-[6.4.0.0(1,3)]dodecan-9-one.

The title compound, C16H24O3, is built up from three fused rings, a six-membered, a seven-membered and a three-membered ring. The absolute configuration of the title compound was determined as (1R,3S,8R,11R) based on the synthetic pathway. The six-membered ring has an half-chair conformation whereas the seven-membered ring displays a boat conformation. In the cyrstal, C-H⋯O hydrogen bonds build up a two-dimensional network parallel to (0 0 1). The crystal studied was an inversion twin with a minor twin component of 34%.