One-pot Three-component Approach Research Articles

A potent therapeutic scaffold fusing quinazolinone/melatonin for future colorectal cancer interventions: design, one-pot synthesis, biological and ADME-tox modeling studies

AbstractColorectal cancer is one of the most incident and lethal cancers in the world. The search for new compounds to treat this disease is being motivated by the occurrence of side effects and the rising in the resistance to chemotherapy. We synthesized a new class of conjugates bearing quinazolinone and melatonin which were prepared in good yields (63–93%) through one-pot three-component approach. quinazolinone/melatonin conjugates were proved against SW480 human colorectal adenocarcinoma cells and non-malignant colonic cells (NCM460). The cytotoxic and antiproliferative activities were determined through the sulforhodamine B assay. Compounds 1f, 1g and 1i–l displayed the best activity, being hybrids 1i–l the most selective against malignant cells, causing either a cytostatic and/or cytotoxic effect with evident morphological changes. Moreover, a theoretical drug-like/pharmacokinetics/toxicological study suggested that the hit-promising compounds 1i and 1j would have a great chance to advance to further preclinical studies as anti-cancer therapeutic candidate for oral oncological management. Our study evidently identified the potency of these quinazolinone/melatonin hybrids to be a prototype drug for further investigations toward novel therapeutics treatments of colorectal cancer.

Photomediated One-Pot Three-Component Approach Enables the Formal Direct N-Acylation/Sulfonylation and α-C-H Functionalization of 1,2,3,4-Tetrahydroisoquinoline.

N-Acyl/sulfonyl-α-functionalized 1,2,3,4-tetrahydroisoquinolines (THIQs) are significant structural motifs in organic synthesis and drug discovery. However, the one-pot approach enabling direct difunctionalization of THIQs remains challenging. Herein we report a photomediated one-pot three-component strategy to access N-acyl/sulfonyl-α-functionalized THIQs. This method features the use of oxygen (from air) as the green oxidant, high atom and step economy, and decent structural diversity. The synthetic applicability of the method was further demonstrated via the facile construction of valuable bioactive molecules. Mechanistic studies indicated that oxidation with singlet oxygen and the acceptor-less dehydrogenation were involved in the photoredox process.

A Novel One-Pot Three-Component Approach to Orthoaminocarbonitrile Tetrahydronaphthalenes Using Triethylamine (Et_3N) as a Highly Efficient and Homogeneous Catalyst Under Mild Conditions and Investigating Its Anti-cancer Properties Through Molecular Docking Studies and Calculations

An efficient and environmentally friendly method for the one-pot synthesis of ortho-aminocarbonitrile tetrahydronaphthalenes has been developed in the presence of triethylamine (Et3N) as a homogeneous catalyst. The multicomponent reactions of benzaldehydes, cyclohexanone and malononitrile were carried out under mild conditions to obtain some ortho-aminocarbonitrile tetrahydronaphthalene derivatives. A broad range of structurally diverse benzaldehydes were applied successfully, and corresponding products (4A-L) were obtained in good to excellent yields (87-98%) in very short times (10-25 minutes). The present approach provides several advantages including simple workup, high yields, very mild reaction conditions, short reaction times, little catalyst loading and not requiring specialized equipment. Furthermore, with the help of computational chemistry and drug design methods, the anti-cancer properties of these compounds were studied and investigated. All the synthesized compounds bind to an agonist at the active site of the 3A8P protein, which leads to the inactivation of this protein and produces beneficial effects during cancer treatment. In synthesized compounds, the ligands establish hydrogen bonds with leucine A:728 residues through nitrogen, which has a very special and vital role in biological sciences and pharmaceutical connections. In this study, it was found that these compounds have the potential to become an oral anti-cancer drug.

A Novel One-Pot Three-Component Approach to Orthoaminocarbonitrile Tetrahydronaphthalenes Using Triethylamine (Et_3N) as a Highly Efficient and Homogeneous Catalyst Under Mild Conditions and Investigating Its Anti-cancer Properties Through Molecular Docking Studies and Calculations

An efficient and environmentally friendly method for the one-pot synthesis of ortho-aminocarbonitrile tetrahydronaphthalenes has been developed in the presence of triethylamine (Et3N) as a homogeneous catalyst. The multicomponent reactions of benzaldehydes, cyclohexanone and malononitrile were carried out under mild conditions to obtain some ortho-aminocarbonitrile tetrahydronaphthalene derivatives. A broad range of structurally diverse benzaldehydes were applied successfully, and corresponding products (4A-L) were obtained in good to excellent yields (87-98%) in very short times (10-25 minutes). The present approach provides several advantages including simple workup, high yields, very mild reaction conditions, short reaction times, little catalyst loading and not requiring specialized equipment. Furthermore, with the help of computational chemistry and drug design methods, the anti-cancer properties of these compounds were studied and investigated. All the synthesized compounds bind to an agonist at the active site of the 3A8P protein, which leads to the inactivation of this protein and produces beneficial effects during cancer treatment. In synthesized compounds, the ligands establish hydrogen bonds with leucine A:728 residues through nitrogen, which has a very special and vital role in biological sciences and pharmaceutical connections. In this study, it was found that these compounds have the potential to become an oral anti-cancer drug.

Convenient multicomponent synthesis of furo[3,2-c]coumarins in the promoting medium DIPEAc and assessment of their therapeutic potential through in silico pharmacophore based target screening

A one-pot three-component approach for the synthesis of dihydrofuro[3,2-c]coumarins was developed via the reaction of aryl/hetryl aldehydes, substituted phenacyl bromides and 4-hydroxycoumarin using N,N-diisopropyl ethyl ammonium acetate as the promoting medium.

Short Total Synthesis of (±)-Gelliusine E and 2,3′-Bis(indolyl)ethylamines via PTSA-Catalyzed Transindolylation

A first and short total synthesis of the marine sponge 2,3'-bis(indolyl)ethylamine (2,3'-BIEA) alkaloid (±)-gelliusine E was performed in both a three-step divergent approach and a one-pot three-component approach with an overall yield of up to 58%. A key feature of the novel strategy is PTSA-catalyzed transindolylation of the readily synthesized 3,3'-BIEAs with tryptamine derivatives. The structure of the isolated natural product is revised as protonated (±)-gelliusine E (4'). By design, this modular route allows the rapid synthesis of other members of the 2,3'-BIEA family, for example, (±)-6,6'-bis-(debromo)-gelliusine F and analogues with step economy, operational simplicity, and reduced waste. Furthermore, their cytotoxicity in breast cancer cells was investigated.

Water Extract of Tamarindus Indica Seed Ash: An Agro-Waste Green Medium for One-Pot Three-Component Approach for the Synthesis of 4H-Pyran Derivatives

Herein, a new, bio-mass derived sustainable feedstock was employed for the synthesis of 4H-pyran derivatives. In context of this, water extract of tamarindus indica seed ash (WETSA) has been proven as a reaction media for one-pot three-component reaction between C−H activated carbonyl compound, aryl aldehyde, and malononitrile which acts as a basic catalyst. This novel method offers several advantages such as simple work-up, excellent yield, short reaction time, green reaction conditions, and the reaction even proceeds smoothly without any external promoter. The catalyst was recycled up to four times without significant loss in catalytic activity.

Ompg-C3N4/SO3H organocatalyst-mediated green synthesis of 1,2-dihydro-1-arylnaphtho[1,2-e][1,3] oxazin-3-ones under solvent-free and mild conditions: a fast and facile one-pot three-component approach

In this research, we have described the synthesis of the well-ordered mesoporous graphite carbon nitride (ompg-C3N4) by applying SBA-15 as a potential hard silica template, and the catalytic performance of sulfonated well-ordered mesoporous graphite carbon nitride (ompg-C3N4/SO3H) as an environment‐friendly and efficient polymeric solid acid catalyst was investigated in the one‐pot preparation of 1,2-dihydro-1-arylnaphtho[1,2-e][1,3]oxazin-3-ones. This cyclocondensation reaction was performed in the presence of various substituted aldehydes, urea, and 2-naphthol through mild and efficient solvent-free method. The structure and morphology of ompg-C3N4/SO3H were characterized using various instrumental analysis methods including FT-IR, EDS, FESEM, TEM, TGA, DTG, XRD, and BET. The simplicity of the process, low reaction times, simple workup, high to quantitative yields, avoiding the utilization of organic solvents, and reusability of the as-prepared catalyst are several prominent advantages of this present synthetic method.

KOAc-Catalyzed One-Pot Three-Component 1,3-Dipolar Cycloaddition of α-Diazo Compounds, Nitrosoarenes, and Alkenes: An Approach to Functionalized Isoxazolidines.

A direct, highly efficient KOAc-catalyzed one-pot three-component approach for the preparation of various functionalized isoxazolidines via the 1,3-dipolar cycloaddition reactions of readily accessible diazo compounds, nitrosoarenes, and alkenes has been reported. The cheap and readily available catalyst and starting materials, excellent functional group compatibility, wide substrate scope, high yields, and excellent chemo-, regio-, and diastereoselectivities make this protocol an attractive alternative.

A novel one-pot three-component approach to 4-amino-functionalized spiropyrimidine-2-thiones

A series of 4-amino-functionalized spiropyrimidine-2-thione derivatives were simply produced by the one-pot three-component reaction of alicyclic carbonyl compounds, nitriles containing an acidic methylene, and thiourea in the presence of NaOMe in MeOH.

A one-pot three-component approach to synthesis of novel dihydroxyoxoindeno[1,2-b]pyrrole derivatives

A new class of 2-arylamino-dihydroxyindenopyrroles were prepared by the one-pot multicomponent reaction of ninhydrin, N-methyl-1-(methylthio)-2-nitroethenamine and aromatic amines in EtOH at room temperature. The advantages of this procedure are short reaction times, good to high yields, easy separation of products and good functional group tolerance.

ChemInform Abstract: Catalyst‐Free Convergent Approach for the Synthesis of Spiro(imidazo[2,1‐b][1,3]oxazine‐7,3′‐indoline).

Strategies to address mounting environmental concerns with current approaches include an operationally simple and highly efficient one-pot three-component approach for the synthesis of spiro[imidazo[2,1-b][1,3]oxazine-7,3′-indoline derivatives, which has been developed via Huisgen zwitter ion intermediate. The significant advantages of this protocol are short reaction time, excellent yields, and facile formation of three new bonds in one operation from easily available starting materials.

ChemInform Abstract: Regioselective One‐Pot Three‐Component Synthesis of Quinoline Based 1,2,4‐Triazolo[1,5‐a]quinoline Derivatives.

A one-pot three-component approach for the synthesis of 2-(piperidin-1-yl) quinoline based 1,2,4-triazolo[1,5-a]quinoline derivatives (4a–l) has been described by the reaction of aldehyde (1a–f), methyl 2-cyanoacetate (2) and enaminones (3a–b). Different regioselectivities of the reaction are attained with different catalysts and the highest regioselectivity is achieved by L-proline. This new procedure provides an efficient method to construct fused tricyclic heterocycles containing 1,2,4-triazole analogues. In this regard, we have used the least amount of amphoteric catalyst, like L-proline, ammonium acetate and a mixture of pyrolidine with acetic acid, to obtain the 1,4-dihydroquinoline derivative 5a as a by-product. The salient features of this protocol are the mild reaction conditions, high yield (75–85%) and higher regioselectivity toward the desired products 4a–l. The structures of the title compounds were confirmed by FT-IR, 1H NMR, 13C NMR and mass spectrometry.

Rapid and Efficient Synthesis of Spiro-Oxindoles using Fe3+-Montmorillonite under Ultrasonic Irradiation

A simple and efficient one-pot three-component approach was devised for the synthesis of spiro-oxindoles through the reaction of isatin derivatives, malononitrile and 1,3-dicarbonyl compounds in the presence of modified montmorillonite (Fe3+-mont.) under ultrasonic irradiation. The reaction furnished the desired products in excellent yields (85–95%) and short reaction times (2–7 min).

InBr3 catalyzed tandem construction of C–C, C–O and C–N bonds: a concise, convenient and atom-economical strategy for the synthesis of spiro oxazolidine oxindole derivatives

A versatile, operationally simple and highly efficient one-pot three-component approach for the synthesis of spiro oxazolidine oxindole derivatives has been developed by the domino reaction of isatins, arylacetylenes, and N-tosyl aldimines in acetonitrile catalyzed by InBr3 at ambient temperature. The significant advantages of this protocol are highlighted by excellent yields, cleaner reaction profiles, avoidance of toxic catalyst, broader substrate scope, and successful assembly of three new C–C, C–N and C–O bonds.

Synthesis of 2-(1,2,4-oxadiazol-3-yl)quinazolin-4(3H)-ones from diaminoglyoxime-based nitrones.

Various 2-[5-(aryl)-1,2,4-oxadiazol-3-yl]quinazolin-4(3H)-ones have been synthesized from the reaction of diaminoglyoxime-based nitrones with methyl 2-aminobenzoate or 2-aminobenzamide in the presence of acetic acid at 100 °C. The reaction was extended as a one-pot three-component approach starting from diaminoglyoxime, aldehyde and methyl 2-aminobenzoate.

Regioselective one-pot three-component synthesis of quinoline based 1,2,4-triazolo[1,5-a]quinoline derivatives

A one-pot three-component approach for the synthesis of 2-(piperidin-1-yl) quinoline based 1,2,4-triazolo[1,5-a]quinoline derivatives (4a–l) has been described by the reaction of aldehyde (1a–f), methyl 2-cyanoacetate (2) and enaminones (3a–b).

ChemInform Abstract: A Convenient One‐Pot Three‐Component Approach for Regioselective Synthesis of Novel Substituted Pyrazolo[1,5‐a]pyrimidines Using Fe+3‐Montmorillonite as Efficient Catalyst.

Abstractusing ultrasonic irradiation or conventional thermal conditions

One-pot synthesis of novel pyrido[2,3-d]pyrimidines using HAp-encapsulated-γ-Fe2O3 supported sulfonic acid nanocatalyst under solvent-free conditions

Novel pyrido[2,3-d]pyrimidine derivatives were synthesized through a one-pot three-component approach using HAp-encapsulated-γ-Fe2O3 [γ-Fe2O3@HAp-SO3H] catalyzed condensation of 6-amino-2-(methylthio or ethylthio)pyrimidin-4(3H)-one, Meldrum's acid and aryl aldehydes at 60 °C and under solvent-free conditions. In this protocol the use of nanocatalyst provided a green, useful and rapid method to generate the products in short reaction times and excellent yields (88%–94%).

ChemInform Abstract: Solvent‐Free Synthesis of 1‐Aryl‐1H‐1,2,3,4‐tetrazoles Using FeCl3—SiO2 Catalysis under Conventional and Ultrasound Irradiation Conditions.

AbstractThe first example of an efficient ultrasound promoted one‐pot three‐component approach to the synthesis of 1‐aryltetrazoles (III) (11 examples) is given.