Heterocyclic Frameworks Research Articles

A derivatization-directed three-component synthesis of fluorescent spiro [dihydropyridine-4,3ʹ-indoline

The synthesis of spiro[chromeno[4,3- b]pyrazolo[4,3- e]pyridine-7,3ʹ-indoline]s is achieved via three-component reactions of 5-amino-3-methylpyrazole, 4-aminocoumarin, and isatin derivatives. This protocol provides expedient synthesis of 10-unsubstituted derivatives of the parent heterocyclic spiro framework and does not lead to coumarin ring opening. The synthesis is highly convergent as no by-products are present in the reaction mixtures. The spiro products show violet fluorescence emissions depending on the nature of their substituents.

Iridium(III)-Catalyzed C-H Amidation/Cyclization of NH-Sulfoximines with N-Alkoxyamides: Formation of Thiadiazine 1-Oxides.

The first example of Ir(III)-catalyzed C-H activation/cyclization with N-alkoxyamides as amidation reagents to simultaneously form functionalized thiadiazine 1-oxide derivatives was developed. This one-pot cascade protocol tolerated diverse functional groups and readily constructed various heterocyclic frameworks in moderate to good yield.

Synthesis, characterization, computational and biological studies of nitrothiazole incorporated heterocyclic azo dyes

In this work, we have reported four azo dyes having a heterocyclic framework derived from 2-amino-5-nitrothiazole by a traditional diazo-coupling method in an acidic medium using four different coupling components and characterized them by different spectroscopic techniques. The comparative approach of both the experimental and computational calculations are performed by using DFT/B3LYP at 6-311++G (d, p) basis set with respect to the vibrational and absorption spectra of all the azo dyes. Also, HOMO-LUMO energy and other energy-related global parameters are calculated. The absorption spectra were recorded in the region of 200–700 nm, and the results exhibited a unique absorption in the longer wavelength due to the presence of a nitro group in the moiety as well as solute–solvent interaction. From the quantum chemical calculation values, there is a good correlation that exists between the experimental and computational studies. Furthermore, the antibacterial and antioxidant properties of the azo dyes were evaluated by the disc diffusion method and DPPH assay respectively. The results revealed that all the compounds showed potent inhibitory effect towards the tested pathogenic strains and scavenging activity.

Expedient synthesis of novel antibacterial hydrazono-4-thiazolidinones under catalysis of a natural-based binary ionic liquid.

A library of pyran-2H-one-3-ylmethylidene and chromene-2H-one-3-ylmethylidene derivatives of the titled heterocyclic framework was synthesized from 3-acyl-4-hydroxypyran/chromene-2H-one via sequential reaction with thiosemicarbazide and dialkyl acetylenedicarboxylates. The syntheses were carried out under efficient catalysis of a new binary ionic liquid mixture [L-prolinium chloride][1-methylimidazolium-3-sulfonate] in one pot and solvent-free conditions. Calculations based on density functional theory displayed that the barrier energy for interconversion of the two possible diastereomeric isomers of each product is less than the thermal energy of molecules at room temperature, as only one product can be resolved from a given reaction mixture. This seems to be the case for the previously reported hydrazonothiazolidines. The binary ionic liquid mixture melts at near room temperature and can be considered as a solution of HCl in 1:1 mixture of two zwitterionic species. It proved to be more efficient than its constituents in catalyzing the above synthesis in one-pot operation. Some of the synthesized products have shown pronounced antibacterial activities. The ionic liquid is virtually stable in air and moisture, as can be retrieved several times without appreciable decrease in its catalytic activity.

A review: Chemical and biological activity of chalcones with their metal complex

Chalcone is a fragrant ketone that frames a focal center for an assortment of significant organic mixes, which are altogether known as chalcones. They have various exercises like antibacterial, antifungal, mitigating and against tumor and so on relying upon the replacement made on them. Chalcones are regular item has a place with Flavonoid family. Chalcones are 1, 3-diphenyl-2-propene-1-one, in which two fragrant rings are connected by a three carbon α, β-unsaturated carbonyl framework. Chalcones and their heterocyclic analogs appreciate a scope of organic exercises, for example, antimicrobial, cancer prevention agent, cytotoxic, anticancer, antiprotozoal, antihistaminic, antiulcer and calming exercises which makes these mixes as an extraordinary fascination for examination. Also the bielectrophilic, ketovinyl chain between the two rings is profoundly receptive and goes about as a significant synthetic synthon for building diverse five, six and seven part heterocyclic frameworks containing distinctive hetero molecules like nitrogen, oxygen and sulfur iotas by compressed version with an assortment of binucleophilic reagents.

N‐Directed Pd‐Catalyzed Direct ortho‐Acetoxylation and ortho‐tert‐Butoxylation of 2‐Phenyl‐4H‐benzo[d][1,3]oxazin‐4‐ones via C‐H Activation

AbstractA highly efficient, palladium‐catalyzed protocol for the regioselective ortho‐acyloxylation of 4H‐Benzo[d][1,3]oxazin‐4‐ones and various other heterocycles which includes indoline, 3,4‐dihydro‐2H‐benzo[b][1,4]oxazine, and 1‐methyl‐3‐phenylquinoxalin‐2(1H)‐one has been developed using C−H activation strategy. The protocol exploits the directing group property of nitrogen present in the heterocyclic framework to introduce the acyloxyl group onto heterocyclic compounds with excellent regioselectivity. The developed method offers a wide substrate and excellent functional group tolerance.

Synthesis of Functionalized Tetrahydropyridines by SnCl4 -Mediated [4+2] Cycloaddition between Donor-Acceptor Cyclobutanes and Nitriles.

Cycloadditions of strained carbocycles promoted by Lewis acids are powerful methods to construct heterocyclic frameworks. In fact, the formal [3+2] cycloadditions of donor-acceptor (DA) cyclopropanes with nitriles has seen particular success in synthesis. In this work, we report on the first [4+2] cycloaddition of nitriles with DA cyclobutanes by Lewis acid activation. Tetrahydropyridine derivatives were obtained in up to 91 % yield from various aryl-activated cyclobutane diesters and aliphatic or aromatic nitriles.

Aza-Annulation of 1,2,3,4-Tetrahydro-β-carboline Derived Enaminones and Nitroenamines: Synthesis of Functionalized Indolizino[8,7-b]indoles, Pyrido[1,2-a:3,4-b']diindoles, Indolo[2,3-a]quinolizidine-4-ones and Other Tetrahydro-β-carboline Fused Heterocycles.

Aza-annulation of novel 1,2,3,4-tetrahydro-β-carboline derived enaminones and nitroenamines with various 1,2- and 1,3-bis electrophiles, such as oxalyl chloride, maleic anhydride, 1,4-benzoquinone, 3-bromopropionyl chloride, itaconic anhydride, and imines (from formaldehyde and primary amines), has been investigated. These methodologies provide simple one-step pathways for efficient construction of highly functionalized tetrahydro-β-carboline 1,2-fused, five- and six-membered heterocyclic frameworks, such as indolizino[8,7-b]indoles, pyrido[1,2-a:3,4-b′]diindoles, indolo[2,3-a]quinolizidines, and pyrimido[1′,6′:1,2]pyrido[3,4-b]indoles, which are core structures of many naturally occurring indole alkaloids with diverse bioactivity.

Ni-Catalyzed Reductive Liebeskind-Srogl Alkylation of Heterocycles.

Herein we present a Ni-catalyzed alkylation of C–SMe with alkyl bromides for the decoration of heterocyclic frameworks. The protocol, reminiscent to the Liebeskind–Srogl coupling, makes use of simple C(sp2)–SMe to be engaged in a reductive coupling. The reaction is suitable for a preponderance of highly valuable heterocyclic motifs. In addition to cyclic bromides, noncyclic alkyl bromides are well accommodated with exquisite levels of retention over isomerization. The protocol is scalable and permits orthogonal couplings in the presence of other functionalization handles.

Brønsted Acid-Catalyzed (4 + 3) Cyclization of N, N'-Cyclic Azomethine Imines with Isatoic Anhydrides.

A Brønsted acid-catalyzed (4 + 3) cyclization of N, N'-cyclic azomethine imines with isatoic anhydrides has been discovered, which constructs seven-membered nitrogenous heterocyclic frameworks with overall high yields (up to 98% yield). This reaction represents a rarely reported (4 + 3) cyclization of N, N'-cyclic azomethine imines, which involves the reassembly of a C-N bond. In addition, this reaction has also accomplished the unprecedented (4 + 3) cyclization of isatoic anhydrides.

Organocatalytic Regiodivergent C-C Bond Cleavage of Cyclopropenones: A Highly Efficient Cascade Approach to Enantiopure Heterocyclic Frameworks.

Here a highly efficient cascade approach is reported that combines a cycloaddition reaction with a regioselective strain-release process to afford diverse heterocyclic frameworks through bifunctional catalysis. The cooperation of hydrogen-bonding network activation and a regiodivergent strain-assisted effect is the key to promoting this complex chemical transformation, leading to the generation of two different ring systems in high yields with excellent stereoselectivities. The reaction proceeded by a mechanism involving a "spring-loaded" intermediate with switchable C-C bond cleavages achieved by controllable ring-strain release. This reaction was also amenable to gram scale synthesis with only 0.1 mol % catalyst loading.

Modulation of S. aureus and P. aeruginosa biofilm: an in vitro study with new coumarin derivatives.

Coumarin is an important heterocyclic molecular framework of bioactive molecules against broad spectrum pathological manifestations. In the present study 18 new coumarin derivatives (CDs) were synthesized and characterized for antibiofilm activity against two model bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa. It was observed that all the CDs executed significant effect in moderating activities against both planktonic and biofilm forms of these selected bacteria. Hence, to interpret the underlying probable reason of such antibiofilm effect, in-silico binding study of CDs with biofilm and motility associated proteins of these organisms were performed. All CDs have shown their propensity for occupying the native substrate binding pocket of each protein with moderate to strong binding affinities. One of the CDs such as CAMN1 showed highest binding affinity with these proteins. Interestingly, the findings of in-silico studies coincides the experimental results of antibiofilm and motility affect of CDs against both S. aureus and P. aeruginosa. Moreover, in-silico studies suggested that the antibiofilm activity of test CDs may be due to the interference of biofilm and motility associated proteins of the selected model organisms (PilT from P. aeruginosa and TarK, TarO from S. aureus). The detailed synthesis, characterization, methodology and results of biological screening along with computational studies have been reported. This study could be of greater interest in the context of the development of new anti-bacterial agent in the future.

Cu-catalyzed Asymmetric Dearomative [3 + 2] Cycloaddition Reaction of Benzazoles with Aminocyclopropanes

Summary Heterocycles are a very important class of compounds that exist extensively as structural cores in natural products and biologically active molecules. Catalytic asymmetric dearomatization (CADA) is an efficient strategy for the construction of chiral fused- or spiro-heterocycles from simple planar aromatic compounds. Herein, we report the development of enantioselective dearomative [3 + 2] cycloaddition reactions of benzazoles with aminocyclopropanes via kinetic resolution. In the presence of a copper complex, derived from Cu(OTf)2 and bisoxazoline, a series of hydropyrrolo-benzazole derivatives containing quaternary stereogenic centers were obtained in high yields (up to 99%) with excellent enantioselectivity (up to 99% enantiomeric excess [ee]). With the same catalytic system, 2-amino cyclopropane-1,1-dicarboxylates with a high enantiomeric purity (up to 98% ee) were also obtained by an efficient kinetic resolution (s values of up to 95). In addition, the utility of this method was showcased by the facile transformation of products into several important heterocyclic frameworks, including pyrrolo-benzothiazine and 1,5-benzothiazepine.

Tetrathiafulvalene Dimer Merged with a Binuclear Ring of Sn and Sb: Synthesis and Molecular Structures Induced by Heteroatoms

In this study, we describe the synthesis and characterization of dimeric tetrathiafulvalene (TTF) derivatives that are doubly bridged by Sn (1) and Sb (2a) atoms as a new class of organic‐inorganic hybrid compounds able to provide enhanced dimensionality in the solid state. The antimony heterocyclic framework was constructed by a simple Sn–Sb metal exchange reaction of a 1,4‐distannine moiety with p‐tolyl antimony dichloride (p‐tolSbCl2). Compound 2a was obtained in cis and trans forms as a stable configurational isomer. From X‐ray crystallographic analysis, there were three conformational isomers in which the tolyl rings were directed in the endo or exo direction. Crystal packing revealed a supramolecular three‐dimensional network through intermolecular short contacts of Sb···S and Sb···π. These packing forces gave a trans‐2aexo–exo conformation in the crystal, although the theoretical calculations predict its instability compared with other conformers. Cyclic voltammetry (CV) measurements of 1 and cis/trans‐2a revealed two pairs of reversible redox processes corresponding to the formation of TTF/TTF·+ and TTF·+/TTF2+. Furthermore, CV of cis/trans‐2a also revealed the reduction waves derived from the reduction of SbIII. Dicationic and tetracationic species were prepared by chemical oxidation, and their electronic structures were also investigated by electronic spectroscopy.

Design, synthesis and evaluation of novel 2,2-dimethyl-2,3-dihydroquinolin-4(1H)-one based chalcones as cytotoxic agents

We designed and synthesised a series of novel chalcones, incorporating the heterocyclic framework of 2,2-dimethyl-2,3-dihydro-4(1H)-quinolinone, which was prepared via Sonogashira coupling of a substituted orthoaniline under aqueous conditions using Pd catalysis followed by acid-mediated cyclisation. The compounds were screened against the NCI-N87 and DLD-1 cancer cell lines, with most compounds showing low micromolar cytotoxic activity.

Asymmetric [3 + 3] Annulation of Copper-Allenylidenes with Pyrazolones: Synthesis of Chiral 1,4-Dihydropyrano[2,3- c]pyrazoles.

The copper-catalyzed asymmetric [3 + 3] annulation of ethynyl benzoxazinanones with pyrazolones has been achieved, providing simple access to 1,4-dihydropyrano[2,3- c]pyrazole derivatives in moderate to excellent yields with excellent enantioselectivities (up to 99% ee). Compared with previous annulation reactions of copper-allenylidenes from ethynyl benzoxazinanones, the current reaction fused the three carbon atoms of the propargyl moiety into a heterocyclic framework.

Enantiomeric Pairs of Meroterpenoids with Diverse Heterocyclic Systems from Rhododendron nyingchiense.

Eight enantiomeric pairs of new meromonoterpenoids (1a/1b-8a/8b) and four known compounds (9-12) were isolated from Rhododendron nyingchiense. Their structures were established by spectroscopic methods, quantum chemical calculations, and X-ray crystallography. The enantiomeric pairs were acquired from scalemic mixtures by chiral-phase HPLC and showed diverse heterocyclic frameworks. Compounds 1a/1b possess a rare 6/7/5/5 heterocyclic system, and 2a/2b incorporate a new 6/6/3/5 heterocyclic system featuring a quinone motif. Compounds 3a/3b represent the first meroterpenoids with a 6/6/5 ring system from the Rhododendron genus. Putative biosynthetic pathways of these compounds are proposed. Compounds 1b, 2a-4a, 8a, 8b, and 11 exhibited weak inhibitory effects on PTP1B, with IC50 values ranging from 5.7 ± 0.5 to 61.0 ± 4.8 μM.

Palladium-Catalyzed Cyclocarbonylation of Pyridinylated Vinylogous Amides and Ureas to Generate Ring-Fused Pyridopyrimidinones.

As part of a program aimed at generating new heterocyclic frameworks for medicinal chemistry exploration, an efficient approach to the assembly of novel ring-fused pyridopyrimidinones was undertaken. Specifically, a collection of 11 H-pyrido[2,1- b]quinazoline-1,11(2 H)-diones and 2,3-dihydropyrido[1,2- a]pyrrolo[3,4- d]pyrimidine-1,10-diones was generated via a palladium-catalyzed, pyridine-directed, cyclocarbonylation of 2-pyridyl-linked vinylogous amides and ureas in yields of up to 90%.

Synthesis of fused 3-amino-1,2,4-triazoles via sequential addition of aryl hydrazines to isothiocyanates and I2-mediated cyclodesulfurization

A variety of fused 3-amino-1,2,4-triazole derivatives were synthesized via addition of aryl hydrazines to isothiocyanates followed by I2-mediated oxidative cyclodesulfurization. This transition-metal-free synthetic process provides facile access to 1,2,4-triazolo[4,3-a]pyridines and related heterocyclic frameworks bearing a 3-amino substituent from readily accessible substrates in an efficient and scalable fashion.

Palladium-Catalyzed Ullmann Cross-Coupling of β-Iodoenones and β-Iodoacrylates with o-Halonitroarenes or o-Iodobenzonitriles and Reductive Cyclization of the Resulting Products To Give Diverse Heterocyclic Systems.

The palladium-catalyzed Ullmann cross-coupling of β-iodoenones and β-iodoacrylates such as 5 (X = I) with o-halonitroarenes and o-iodobenzonitriles including 2 affords products such as compound 7. These can be engaged in a range of reductive cyclization reactions leading to heterocyclic frameworks such as 3,4-benzomorphan derivative 43.