Oxygen-containing Heterocycles Research Articles

Exploring Novel Benzopyran Derivatives as Antitubercular Agents

Background: Tuberculosis (TB) remains a significant global health concern, necessitating the exploration of novel therapeutic agents. Reported antitubercular activities of previously synthesized benzopyran and other oxygen-containing heterocycles motivate us to synthesize and evaluate the antitubercular potential of benzopyran derivatives. Objective: The aim of this study was to combine two scaffolds; one is coumarin (benzopyran-2-one), and another one is piperazine, as both are found in anti-tubercular derivatives. Methods: Through a four-step synthetic approach, compounds SM1-SM10 were synthesized. These derivatives were subsequently evaluated for their in vitro anti-tubercular potential using the resazurin microtiter assay (REMA), with isoniazid as the standard (MIC 0.25 to 0.5μg/mL). Results: Among the synthesized compounds, SM2 and SM8 demonstrated remarkable antitubercular activity, with MICs of 4 and 6μg/mL, respectively. Notably, these MIC values are considerable for the further development of benzopyran derivatives as potent antitubercular agents. Conclusion: Outcomes underscore the potential of benzopyran derivati ves as valuable assets in TB drug discovery, warranting further exploration and development.

Styrylchromones: Biological Activities and Structure-Activity Relationship.

Styrylchromones (SC) are a group of oxygen-containing heterocyclic compounds, which are characterized by the attachment of a styryl group to the chromone core. SC can be found in nature or can be chemically synthesized in the laboratory. As their presence in nature is scarce, the synthetic origin is the most common. Two types of SC are known: 2-styrylchromones and 3-styrylchromones. However, 2-styrylchromones are the most common, being more commonly found in nature and which chemical synthesis is more commonly described. A wide variety of SC has been described in the literature, with different substituents in different positions, the majority of which are distributed on the A- and/or B-rings. Over the years, several biological activities have been attributed to SC. This work presents a comprehensive review of the biological activities attributed to SC and their structure-activity relationship, based in a published literature search, since 1989. The following biological activities are thoroughly revised and discussed in this review: antioxidant, antiallergic, antiviral, antibacterial, antifungal, anti-inflammatory and antitumoral, affinity and selectivity for A3 adenosine receptors, neuroprotective, and α-glucosidase inhibition. In general, SC are composed by a promising scaffold with great potential for the development of new drugs.

Green synthesis of coumarins via Pechmann condensation catalyzed by reusable functionalized organosilica

Oxygen-containing heterocycles hold diverse uses in biology and organic chemistry. Herein, a method utilizing a functionalized pyridinium protic ionic liquid framework (PMO-Py-IL) was developed for the solvent-free Pechmann synthesis of coumarins from phenols and ethyl or methyl acetoacetate. High to excellent product yields were obtained under the investigated conditions. PMO-Py-IL remained stable and reactive across multiple reaction runs (up to 12 times), showcasing its stability and efficiency. The ionic nature of the catalyst can increase the polarity of the reaction mixture, leading to improved solubility of reactants and facilitating their interaction. This ultimately stabilizes the intermediates and accelerates the reaction, resulting in higher yields of the desired product. This can further speed up the reaction and increase the yield of the desired product. The proposed approach provides an efficient, simple and easy work-up methodology for coumarin synthesis, with outstanding nanocatalyst's reusability, offering environmental and economic advantages.

Nonoxidovanadium(IV) Complex-Catalyzed Synthesis of 2-Amino-3-cyano-4H-pyrans/4H-chromenes, Biscoumarins, and Xanthenes under Green Conditions.

Reaction of [VIVO(acac)2] (Hacac = acetylacetone) with a Mannich base, N,N,N',N'-tetrakis(2-hydroxy-3,5-di-tert-butyl benzyl)-1,2-diaminoethane (H4L, I) in a 1:1 molar ratio in MeOH, leads to the formation of the nonoxidovanadium(IV) complex [VIVL] (1). Air stable complex 1 has been characterized using various spectroscopic techniques, DFT calculations, and single-crystal X-ray studies. 1 adopts distorted octahedral geometry where ligand coordinates through all coordination functionalities available. This complex has been used as a catalyst in the one-pot, three-component synthesis of 2-amino-3-cyano-4H-pyrans using 1,3-dicarbonyls (1,3-cyclohexanedione, dimedone, barbituric acid, and 4-hydroxycoumarin), malononitrile, and various substituted aromatic aldehydes in equimolar amounts employing ethanol as a green solvent. The catalytic reaction revealed that the multicomponent synthesis of 4H-pyrans and chromenes is greatly influenced by both types of 1,3-dicarbonyl compound employed and the nature of the substituent on the aromatic ring of the aldehyde. Synthesized catalyst has also been used in the synthesis of pharmacologically relevant oxygen-containing heterocycles, specifically, 1,8-dioxo-octahydro-1H-xanthenes and biscoumarins. The possible mechanism for the synthesized one-pot, multicomponent product has been proposed by isolating intermediate(s) generated during synthesis.

Study on pyrolysis characteristics of Gonghe oil shale using Py-GC/MS under different atmospheres

ABSTRACT Taking Gonghe oil shale as raw material, the rapid pyrolysis experiment was carried out using the Py-GC/MS device under different atmospheres. The effects of different pyrolysis atmospheres on the rapid pyrolysis products of Gonghe oil shale were studied. The results show that the H2 atmosphere can not only increase the content of saturated hydrocarbons and reduce the content of unsaturated hydrocarbons but also reduce the content of oxygen-containing heterocyclic compounds. This may be because more H free radicals under the H2 atmosphere are produced to react with the free radical fragments formed by kerogen decomposition. The coupling between H free radicals and free radical fragments can prevent the polymerization among macromolecular free radicals and inhibit the generation of heavy byproducts, which can promote the kerogen pyrolysis and increase the release of volatile matter. In addition, the pyrolysis atmosphere is conducive to the deoxygenation of oxygen-containing heterocyclic compounds to a certain extent.

Cobalt(II)-Catalyzed Proficient Synthesis of Enaminones from Aryl Alkenes and Amines

AbstractA simple, cost-effective, and modular strategy has been developed to synthesize synthetically and pharmaceutically active enaminones by oxidative amination of aryl alkenes with amines and CHCl3, using tert-butyl hydroperoxide as an oxidant. We describe the synthesis of enaminones from vinyl arenes and sterically hindered N,N-diisopropylethylamine (DIPEA) by employing an Earth-abundant cobalt salt as a catalyst within a very short reaction period for the first time. Furthermore, nitrogen- and oxygen-containing heterocyclic compounds have been synthesized from these highly functionalized enaminones. Moreover, various control experiments, such as radical trapping reaction, along with a Hammett analysis with various types of substituents on the styrene ring unraveled the detailed mechanism of this reaction pathway.

Unusual Cascade Reactions of 8-Acetoxy-6-hydroxymethyllimonene with Salicylic Aldehydes: Diverse Oxygen Heterocycles from Common Precursors.

Chiral oxygen-containing heterocyclic compounds are of great interest for the development of pharmaceuticals. Monoterpenes and their derivatives are naturally abundant precursors of novel synthetic chiral oxygen-containing heterocyclic compounds. In this study, acid catalyzed reactions of salicylic aldehydes with (-)-8-acetoxy-6-hydroxymethyllimonene, readily accessible from α-pinene, leads to the formation of chiral polycyclic products of various structural types. Three of the six isolated chiral heterocyclic products obtained from salicylic aldehyde contain previously unknown polycyclic ring types. Having carried out the reaction in the presence of Brønsted or Lewis acids (Amberlyst 15, trifluoromethanesulfonic acid, trifluoroacetic acid and boron trifluoride etherate) or aluminosilicates (montmorillonite K10, halloysite nanotubes), we found that the nature of products depends on the catalyst as well as the reaction conditions (reaction time, reactant ratio, presence or absence of solvent). Detailed mechanistic insight on the complex cascade reactions for product formation is provided with extensive experimental and quantum mechanical computational studies.

Exploitation of ninhydrin core towards spiropyranocoumarin and benzofuranyl coumarin: Synthesis, crystal structure and self-assembly

Pyrano and furanocoumarins are oxygen-containing heterocycles frequently found in natural products and biologically active molecules. In the present work, ninhydrin core is employed for the first time as the pivotal framework to construct benzopyrano/furano coumarin skeleton. It has been found that substrates like phenol, p-/m-cresol, m-methoxyphenol, p-chlorophenol etc. reacted with ninhydrin-4-hydroxycoumarin adduct 3 in AcOH/H2SO4 to furnish a new class of spiropyranocoumarins 5a-f via condensation/cyclization sequence. Under similar conditions, reaction of adduct 3 with 3,5-dihydroxybenzoic acid delivered benzofuranyl coumarin 6 through ring closing/ring opening mechanism. Structures of the synthesized compounds were characterized by IR, 1H and 13C NMR spectroscopy. Single crystal X-ray diffraction study revealed that spiropyranocoumarin 5b self-assembled to form sheet-like arrangement. However, benzofuranyl coumarin 6 was found to display helix-like architecture in the crystalline state. Scanning electron microscopy (SEM) images of compound 5b exhibited flat fibrillar morphology, whereas compound 6 revealed formation of vesicular structure. These types of small heterocyclic molecules are decent candidates for producing promising soft materials.

Discovery of Di(het)arylmethane and Dibenzoxanthene Derivatives as Potential Anticancer Agents.

A family of bifunctional dihetarylmethanes and dibenzoxanthenes is assembled via a reaction of acetals containing a 2-chloroacetamide moiety with phenols and related oxygen-containing heterocycles. These compounds demonstrated selective antitumor activity associated with the induction of cell apoptosis and inhibition of the process of glycolysis. In particular, bis(heteroaryl)methane containing two 4-hydroxy-6-methyl-2H-pyran-2-one moieties combine excellent in vitro antitumor efficacy with an IC50 of 1.7 µM in HuTu-80 human duodenal adenocarcinoma models with a high selectivity index of 73. Overall, this work highlights the therapeutic potential of dimeric compounds assembled from functionalized acetals and builds a starting point for the development of a new family of anticancer agents.

Ketyl Radical Enabled Synthesis of Oxetanes

AbstractOxetanes, 4-membered oxygen-containing heterocycles, were identified to have pharmaceutical applications after the discovery of the chemotherapeutic drug taxol (Paclitaxel) and its analogues. Furthermore, oxetanes have been identified as bioisosteres for several common functional groups and are present in a number of natural products. However, oxetanes are one of the least common oxygen-containing heterocycles in active pharmaceutical ingredients on the market, which can be attributed, in part, due to challenges with their synthesis. Previous strategies rely on nucleophilic substitutions or [2+2]-cycloadditions, but are limited by the stepwise buildup of starting material and limitations in scope resulting from requirements for activated substrates. To address these limitations, we envisioned activating simple carbonyls to their corresponding α-oxy iodides to promote ketyl radical formation. These radicals can then undergo atom-transfer radical addition with alkenes followed by one-pot nucleophilic substitution to produce oxetanes. Herein, we present a proof-of-principle of this strategy in which fluoroalkyl carbonyls are successfully converted into the corresponding fluoroalkyl oxetanes.

Recent Advances in the Domino Annulation Reaction of Quinone Imines.

Quinone imines are important derivatives of quinones with a wide range of applications in organic synthesis and the pharmaceutical industry. The attack of nucleophilic reagents on quinone imines tends to lead to aromatization of the quinone skeleton, resulting in both the high reactivity and the unique reactivity of quinone imines. The extreme value of quinone imines in the construction of nitrogen- or oxygen-containing heterocycles has attracted widespread attention, and remarkable advances have been reported recently. This review provides an overview of the application of quinone imines in the synthesis of cyclic compounds via the domino annulation reaction.

Development in the Inhibition of Dengue Proteases as Drug Targets.

Viral infections continue to increase morbidity and mortality severely. The flavivirus genus has fifty different species, including the dengue, Zika, and West Nile viruses that can infect 40% of individuals globally, who reside in at least a hundred different countries. Dengue, one of the oldest and most dangerous human infections, was initially documented by the Chinese Medical Encyclopedia in the Jin period. It was referred to as "water poison," connected to flying insects, i.e., Aedes aegypti and Aedes albopictus. DENV causes some medical expressions like dengue hemorrhagic fever, acute febrile illness, and dengue shock syndrome. According to the World Health Organization report of 2012, 2500 million people are in danger of contracting dengue fever worldwide. According to a recent study, 96 million of the 390 million dengue infections yearly show some clinical or subclinical severity. There is no antiviral drug or vaccine to treat this severe infection. It can be controlled by getting enough rest, drinking plenty of water, and using painkillers. The first dengue vaccine created by Sanofi, called Dengvaxia, was previously approved by the USFDA in 2019. All four serotypes of the DENV1-4 have shown re-infection in vaccine recipients. However, the usage of Dengvaxia has been constrained by its adverse effects. Different classes of compounds have been reported against DENV, such as nitrogen-containing heterocycles (i.e., imidazole, pyridine, triazoles quinazolines, quinoline, and indole), oxygen-containing heterocycles (i.e., coumarins), and some are mixed heterocyclic compounds of S, N (thiazole, benzothiazine, and thiazolidinediones), and N, O (i.e., oxadiazole). There have been reports of computationally designed compounds to impede the molecular functions of specific structural and non-structural proteins as potential therapeutic targets. This review summarized the current progress in developing dengue protease inhibitors.

Recent Advances in Oxygen-Containing Heterocycles as Anticancer Agents

Recent Advances in Oxygen-Containing Heterocycles as Anticancer Agents

Inorganic nanoparticles promoted synthesis of oxygen-containing heterocycles

Abstract Since many of the U.S. Food and Drug Administration (FDA)-approved medications contain oxygen-containing heterocyclic molecules, they have been discovered to be quite important. Moreover, over the past 10 years, the field of reusable nanocatalysts has expanded quickly. Therefore, the development of nanotechnology has led to a wide range of applications for nanocatalysis in the synthesis of heterocyclic molecules. The domains of organic chemistry and pharmaceuticals have recently shown a great deal of interest in nanocatalyzed organic processes. Such nanocatalysts enable non-toxic, simpler, environmentally friendly, and more affordable synthetic processes that give only the most desirable compounds in higher quantities and provide simple catalyst separation. As a result of their efficient methods for separating catalysts and products, nanocatalysts were chosen over other catalysts for the synthesis of heterocyclic compounds. This review emphasized the preparation of nanocatalysts, synthetic approaches, and recycling studies of highly excited catalytic systems employed for the synthesis of oxygen-containing heterocyclic compounds.

Synthetic methodologies to access bioactive bis-coumarin scaffold: a recent progress

Abstract Heterocyclics particularly those containing oxygen and nitrogen atoms are unique precursors for the synthesis of various agrochemicals and pharmaceuticals. Bis-coumarins are well-known oxygen-containing heterocycles of great significance. The development of methods to prepare bis-coumarins is of great interest in synthetic organic chemistry because of their versatile importance in medicinal chemistry and chemical biology. Bis-coumarins are well known for their antibiotic, antimicrobial, anti-HIV, and antitumor activity. Due to the vast application of bis-coumarins, the synthesis of these heterocycles has attracted huge interest from researchers. In this review, we have summarized the diverse synthetic routes of bis-coumarin synthesis making use of different catalysts and solvents under versatile reaction conditions.

Synthesis of Nitrogen- and Oxygen-Containing Heterocycles Catalysed by Metal Nanoparticles Reported in 2022

AbstractThe versatility of aza- and oxa-heterocyclic compounds has garnered significant attention in recent times. A large number of currently approved pharmaceutical products include nitrogen- and oxygen-containing heterocycles. Recent nanotechnological developments have propelled an upsurge in the applications of nanocatalysis for heterocyclic synthesis. Metal nanoparticles (MNPs) have emerged as promising catalysts for the synthesis of aza- and oxa-heterocycles owing to their unique physicochemical properties. Various MNPs including gold, silver, nickel and palladium have been evaluated for their catalytic activities in different reaction types, including cyclisation, coupling, hydrogenation and oxidative transformations. The MNPs have exhibited remarkable catalytic efficiency when utilised under optimal conditions. These catalysts have showcased high reusability and recyclability, yielding satisfactory amounts of the desired heterocyclic compound. The present work provides a detailed overview of recent advances in the area of MNP-assisted synthetic construction of aza- and oxa-heterocycles, published during the previous calendar year, 2022. The review serves as a valuable resource and also paves the way for future investigations in the development of novel catalytic strategies for heterocycle synthesis.1 Introduction2 Nanocatalysis3 Aza- and Oxa-Heterocycle Synthesis Catalysed by MNPs3.1 AuNPs3.2 CuNPs3.3 CoNPs3.4 FeNPs3.5 NiNPs3.6 PdNPs3.7 PtNPs3.8 SiNPs3.9 ZnNPs3.10 Bimetallic NPs3.11 Other MNPs4 Summary and Outlook

Synthesis of an 8-membered oxygen-containing benzo-fused heterocycle using flow technologies – an exercise in undertaking research with sustainability as a driver

Due to their natural abundance and biological properties, benzo-fused heterocycles are attractive targets in the field of drug discovery.

Controlled generation of ortho-quinone methides and (4+3) cyclization with 2-indolylalcohols by dual photoredox/Brønsted acid relay catalysis

Given the significance of oxacyclic frameworks in molecular scaffolds and drug discovery, it is intriguing to precisely construct and manipulate such ring systems in chemical research. In this area, the intermolecular, multicomponent cyclization for the synthesis of diversely substituted seven-membered ring oxacycles under simple conditions is still a challenge. Here, we report a dual photoredox/Brønsted acid relay catalytic strategy for in situ generation of ortho-quinone methides and subsequent (4 ​+ ​3) cyclization with 2-indolylalcohols. In this one-pot multicomponent reaction, two C–C and one C–O bonds are formed, providing de novo access to various biologically important indole-fused, oxygen-containing seven-membered heterocycles. By virtue of a chiral phosphoric acid, an asymmetric version can also be achieved with good to excellent levels of enantioselectivity (up to 96:4 er).

Visible-light promoted oxidative annulation of 2-naphthols with phenylglyoxal monohydrates toward hydroxy-naphthofuranone and its derivatives.

A highly efficient and innovative method involving base-mediated oxidative annulation between 2-naphthols and phenylglyoxal monohydrate under visible light irradiation has been successfully developed. This method leads to the formation of oxygen-containing heterocyclic compounds, particularly hydroxy-naphthofuranone derivatives, encompassing a unique quaternary carbon center. An X-ray diffraction study has unambiguously confirmed the structure of one such derivative. In particular, water molecules in this reaction serve various functions as a solvent, reagent, and additive, with the conversion of the process found to be influenced by the volume of water present. This atom-economical approach demonstrates tolerance for different substituents in both phenylglyoxal monohydrate and 2-naphthol, enabling the synthesis of a variety of naphthofuranones in satisfactory to good yields. The formation of a naphthofuranium cationic intermediate under acidic circumstances enables the formation of C-C or C-O bonds with a wide range of aromatic or alcoholic nucleophilic partners. Furthermore, the identification and generation of pinacol-type starting precursors from these naphthofuranone derivatives enable the synthesis of highly regioselective naphthofuran derivatives.

Rhodium-catalyzed intramolecular cyclization for synthesizing thiodihydropyrans.

Addressing the challenge of constructing multi-substituted dihydropyrans, we present an efficient synthesis method for oxygen-containing heterocycles. Using thiones and metal carbenes, we employed xanthate and triazole to intramolecularly synthesize dihydropyran or dihydrofuran compounds. 1,2-Hydride migration was inhibited, and thiodihydropyrans were obtained in excellent yields. A mechanism proceeding through a Rh-carbene intermediate is proposed for the multi-substituted dihydropyrans synthesis.