Domino Knoevenagel hetero-Diels Alder Reaction Research Articles

Synthesis and Biological Evaluation of some Novel Pyrano[2,3-<i>d</i>]Pyrimidine Derivatives

The synthesis of novel Pyrano[2,3-d]pyrimidine derivatives, had been synthesized by three component domino Knoevenagel hetero Diels-Alder reaction. The products were assayed for their in vitro biological assay antibacterial activity against with two Gram-positive bacteria Staphylococcus aureus MTCC-96, Streptococcus pyogenes MTCC 443, two Gram-negative bacteria Escherichia coli MTCC 442, Pseudomonas aeruginosa MTCC 441 and three fungal strains Candida albicans MTCC 227, Aspergillus Niger MTCC 282, Aspergillus clavatus MTCC 1323 taking ampicillin, chloramphenicol, ciprofloxacin, norfloxacin, nystatin, and griseofulvin as standard drugs. Among the various synthesized heterocyclic compounds, 1b, 1c and 1g are display broad spectrum antibacterial and antifungal activities against both gram-positive and gram-negative bacteria as compared with standard drugs.

Synthesis and Biological Evaluation of some Novel Pyrano[2,3-<i>d</i>]Pyrimidine Derivatives

The synthesis of novel Pyrano[2,3-d]pyrimidine derivatives, had been synthesized by three component domino Knoevenagel hetero Diels-Alder reaction. The products were assayed for their in vitro biological assay antibacterial activity against with two Gram-positive bacteria Staphylococcus aureus MTCC-96, Streptococcus pyogenes MTCC 443, two Gram-negative bacteria Escherichia coli MTCC 442, Pseudomonas aeruginosa MTCC 441 and three fungal strains Candida albicans MTCC 227, Aspergillus Niger MTCC 282, Aspergillus clavatus MTCC 1323 taking ampicillin, chloramphenicol, ciprofloxacin, norfloxacin, nystatin, and griseofulvin as standard drugs. Among the various synthesized heterocyclic compounds, 1b, 1c and 1g are display broad spectrum antibacterial and antifungal activities against both gram-positive and gram-negative bacteria as compared with standard drugs.

Efficient access to novel tetra- and pentacyclic dihydroquinolin-2-ones by catalyst-free domino Knöevenagel hetero-Diels–Alder reactions from N-(2-formylphenyl)-N-methylcinnamamides and cyclic 1,3-dicarbonyls in water

An efficient catalyst-free synthesis of novel annulated hybrid derivatives of two known scaffolds, dihydroquinolinone and pyranopyranone, pyranopyrimidinedione, pyranocoumarin or chromenone is described. N-(2-Formylphenyl)-N-methylcinnamamides underwent a one-pot domino Knoevenagel hetero-Diels–Alder reaction with dimedone, N,N-dimethylbarbituric acid, 1,3-indanedione, 4-hydroxycoumarins and 4-hydroxy-6-methyl-2H-pyran-2-one in water, affording the desired tetra and pentacyclic pyranoquinolinones in excellent yields.

Microwave-induced domino-Knoevenagel-hetero Diels–Alder reaction—an easy route to di[1]benzopyrano[2,3-b:4′,3′-d]pyridine

MW-irradiation of a well-ground equimolar mixture of 2-(N-alkynyl-N-aryl)aminochromone-3-carbaldehyde and dimedone underwent domino-Knoevenagel-hetero Diels–Alder (DKHDA) reaction for nonterminal alkynes, whereas conventional heating of the above reaction mixture in ethanol in the presence of pyridine accomplished alkyne-carbonyl metathesis (ACM) reaction or both ACM and DKHDA reaction. Here is the first example of an organo-catalyzed ACM reaction.

Synthesis of new chlorin e6 trimethyl and protoporphyrin IX dimethyl ester derivatives and their photophysical and electrochemical characterizations.

In view of increasing demands for efficient photosensitizers for photodynamic therapy (PDT), we herein report the synthesis and photophysical characterizations of new chlorin e6 trimethyl ester and protoporphyrin IX dimethyl ester dyads as free bases and Zn(II) complexes. The synthesis of these molecules linked at the β-pyrrolic positions to pyrano[3,2-c]coumarin, pyrano[3,2-c]quinolinone, and pyrano[3,2-c]naphthoquinone moieties was performed by using the domino Knoevenagel hetero Diels-Alder reaction. The α-methylenechromanes, α-methylenequinoline, and ortho-quinone methides were generated in situ from a Knoevenagel reaction of 4-hydroxycoumarin, 4-hydroxy-6-methylcoumarin, 4-hydroxy-N-methylquinolinone, and 2-hydroxy-1,4-naphthoquinone, respectively, with paraformaldehyde in dioxane. All the dyads as free bases and as Zn(II) complexes were obtained in high yields. All new compounds were fully characterized by 1D and 2D NMR techniques, UV/Vis spectroscopy, and HRMS. Their photophysical properties were evaluated by measuring the fluorescence quantum yield, the singlet oxygen quantum yield by luminescence detection, and also the triplet lifetimes were correlated by flash photolysis and intersystem crossing (ISC) rates. The fluorescence lifetimes were measured by a time-correlated single photon count (TCSPC) method, fluorescence decay associated spectra (FDAS), and anisotropy measurements. Magnetic circular dichroism (MCD) and circular dichroism (CD) spectra were recorded for one Zn(II) complex in order to obtain information, respectively, on the electronic and conformational states, and interpretation of these spectra was enhanced by molecular orbital (MO) calculations. Electrochemical studies of the Zn(II) complexes were also carried out to gain insights into their behavior for such applications.

Trifluoroethanol as an efficient reaction media for the synthesis of pyran skeleton through domino Knoevenagel–hetero-Diels–Alder reaction with non-activated alkynes

Trifluoroethanol as an efficient media for the domino Knoevenagel–hetero-Diels–Alder reaction of O-propargyloxy benzaldehydes as non-activated terminal alkynes with some active methylene compounds has been described. Short reaction time, easy work-up, good to high yields, and mild reaction conditions are advantages of this new media.

ChemInform Abstract: Efficient One‐Pot Synthesis of Precursors of Some Novel Aminochromene Annulated Heterocycles via Domino Knoevenagel—Hetero‐Diels—Alder Reaction.

Abstract An efficient, one-pot synthetic approach to precursors of some new aminochromene/xanthene annulated heterocycles via a tetrabutylammonium hydrogen sulfate–mediated intramolecular domino Knoevenagel–hetero-Diels–Alder reaction is described. The method is general and efficient. The stereochemistry of the product was confirmed by various NMR experiments and single-crystal x-ray diffraction data. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

Synthesis of novel tetra- and pentacyclic benzosultam scaffolds via domino Knoevenagel hetero-Diels–Alder reactions in water

An efficient catalyst-free and diastereoselective synthesis of novel dihydropyrano[2,3-d]pyrimidine and dihydropyrano[3,2-c]chromen-annulated benzosultams is described. A number of (E)-N-(2-formylphenyl)-N-methyl-2-phenylethenesulfonamides were synthesized and underwent a one-pot domino Knoevenagel hetero-Diels–Alder reaction, respectively, with N,N-dimethylbarbituric acid and 4-hydroxycoumarin in water, giving the desired products, in moderate to excellent yields.

Efficient One-Pot Synthesis of Precursors of Some Novel Aminochromene Annulated Heterocycles via Domino Knoevenagel–hetero-Diels–Alder Reaction

An efficient, one-pot synthetic approach to precursors of some new aminochromene/xanthene annulated heterocycles via a tetrabutylammonium hydrogen sulfate–mediated intramolecular domino Knoevenagel–hetero-Diels–Alder reaction is described. The method is general and efficient. The stereochemistry of the product was confirmed by various NMR experiments and single-crystal x-ray diffraction data. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

CuI–Ionic Liquids as Efficient Reaction Media for the Synthesis of Pyran Skeleton via Domino Knoevenagel–Hetero–Diels–Alder Reaction with Unactivated Alkynes

The article describes ionic liquids [bmim][NO3] in the presence of 30% mol CuI as efficient media for the domino Knoevenagel–hetero–Diels–Alder reaction of o-propargyloxy benzaldehydes as unactivated terminal alkynes with some active methylene compounds. Short reaction time, easy workup, good to excellent yields, and mild conditions are advantages of this new media. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.

A domino Knoevenagel hetero-Diels–Alder reaction for the synthesis of polycyclic chromene derivatives and evaluation of their cytotoxicity

A novel octahydrochromeno[4,3-a]xanthen-1(2H)-one derivatives has been prepared using 10mol% dl-proline in ethanol via a domino Knoevenagel hetero-Diels–Alder reaction of alkene-tethered chromene-3-carboxaldehyde with cyclic 1,3-diketones. This is not only the first example on the preparation of highly diastereoselective pentacyclic chromene derivatives from alkene appended chromene-3-carboxaldehyde in one-pot process at ambient temperature but also preliminary evaluation of the cytotoxic activity of these chromene derivatives. Some of these compounds are found to exhibit potent cytotoxicity against two carcinoma cell lines A549 and B-16.

Zirconium oxide (NP) - ionic liquid as an efficient media for the domino Knoevenagel hetero Diels-Alder reaction with unactivated alkynes

Abstract Immobilized ZrO 2 -nanopowder (NP) in ionic liquid and different organic solvents was used as a suitable Lewis-acid for the synthesis of polycyclic heterocycles which contains pyran-based skeletons. Reaction of O -propargylated salicylaldehyde with active methylene compounds in the presence of ZrO 2 -NP in ionic liquid proceeds via domino Knoevenagel hetero Diels-Alder reaction of unactivated alkynes to construct the pyran skeleton. Comparison with different ionic liquids and organic solvents showed that the best results were obtained with 1-butyl-3-methylimidazolium nitrate [bmim][NO 3 ] because of short reaction times and high yields. Carrying out the reaction under these conditions has advantages such as: high yields, short reaction times and easy work-up.

Synthesis of new chromeno-annulated cis-fused pyrano[3,4-c]pyran derivatives via domino Knoevenagel–hetero-Diels–Alder reactions and their biological evaluation towards antiproliferative activity

A new series of chromeno-annulated cis-fused pyrano[3,4-c]pyran derivatives have been synthesized by intramolecular [4 + 2] domino Knoevenagel–hetero-Diels–Alder reactions of 1-oxa-1,3-butadienes derived in situ from 1,3-dicarbonyls/active methylenes and 7-O-prenyl derivatives of 8-formyl-2,3-disubstituted chromenones in the presence of 20 mol% ethylenediamine diacetate (EDDA) in acetonitrile under reflux conditions in good to excellent yields. The structures were established based on spectroscopic data, and were further confirmed by X-ray diffraction analysis. These compounds were evaluated for their anti-proliferative activity using an in vitro MTT cytotoxicity assay. The results clearly demonstrated that compounds 4a, 4b, 4c, 4j, 4k, 4l, 4m and 4n exhibited significant anti-proliferative activity against human A549 lung cancer and non-cancer MRC-5 cell lines along with potent inhibitory activity against human neuroblastoma SK-N-SH cancer cell lines. Among these, compounds 4a, 4b and 4j displayed the most potent anti-proliferative activity against human lung cancer A549 cell lines, while 4a and 4b displayed against neuroblastoma SK-N-SH cancer cell lines when compared to the standard doxorubicin.

Convergent Domino Knoevenagel Hetero‐DielsAlder and Domino Oxidation Hetero‐DielsAlder Reactions Encountered in an Unexpected Formation of Novel 5‐Aryl‐1H‐pyrano[2,3‐d]pyrimidine‐2,4(3H,5H)‐diones and 5‐Aryl‐2,3‐dihydro‐2‐thioxo‐1H‐pyrano[2,3‐d]pyrimidin‐4(5H)‐ones

AbstractConvergent domino Knoevenagel hetero‐DielsAlder and domino oxidation hetero‐DielsAlder reactions, in which both diene and dienophile are formed under the same reaction conditions in situ, are described for the first time, and their application is demonstrated by a one‐pot synthesis of novel 5‐aryl‐1H‐pyrano[2,3‐d]pyrimidine‐2,4(3H,5H)‐diones and 5‐aryl‐2,3‐dihydro‐2‐thioxo‐1H‐pyrano[2,3‐d]pyrimidin‐4(5H)‐ones.

Synthesis and antibacterial property of pyrrolopyrano quinolinones and pyrroloquinolines

Synthesis of a series of novel pyrroloquinolinone and pyrroloquinoline derivatives has been accomplished by intramolecular domino Knoevenagel hetero Diels–Alder reaction and intramolecular imino Diels–Alder reaction. These compounds were evaluated for their antibacterial activity against bacterial pathogens using disc diffusion and broth dilution methods. The efficacy of binding of these compounds to gyrase, an enzyme known to play a key role in bacterial replication is examined by studying its supercoiling and relaxation and also its gene expression using PCR method. The results indicated that most of the synthesised compounds exhibited good antibacterial activity against the microorganisms with MIC values of 5mM and could inhibit gyrase effectively leading to cell death.

Microwave-assisted organocatalytic multicomponent Knoevenagel/hetero Diels–Alder reaction for the synthesis of 2,3-dihydropyran[2,3-c]pyrazoles

A rapid protocol for the multicomponent microwave-assisted organocatalytic domino Knoevenagel/hetero Diels–Alder reaction (DKHDA) has been developed for the synthesis of 2,3-dihydropyran[2,3-c]pyrazoles. The reported procedure could be used for the fast generation of novel substituted 2,3-dihydropyran[2,3-c]pyrazoles with potential anti-tuberculosis activity.

Efficient synthesis of pyrano[2,3- c]coumarins via intramolecular domino Knoevenagel hetero-Diels–Alder reactions

The domino Knoevenagel hetero-Diels–Alder reaction of the O-propargylated salicylaldehydes and 4-hydroxycoumarin leads to pyrano[2,3- c]coumarins 3 and pyrano[2,3- c]chromones 4 in high yield in the presence of CuI as a Lewis acid. In all cases, the reaction was shown to exhibit high regioselectivity and form product 3 as main product.

Design and Synthesis of a Novel Series of Pyranonaphthoquinones as Topoisomerase II Catalytic Inhibitors

On the basis of previous pharmacophore modeling studies of naphthoquinones derivatives, we have designed and synthesized a new set of pyranonaphthoquinones. These compounds were obtained through a direct and highly efficient approach based on an intramolecular domino Knoevenagel hetero Diels-Alder reaction from lawsone (2-hydroxynaphthoquinone) and a variety of aldehydes containing an alkene. The synthesized pyranonaphthoquinones were evaluated against the alpha isoform of human topoisomerase II (hTopoIIalpha). Among the 11 derivatives studied, we found that six of them act as catalytic inhibitors of the enzyme in vitro. These six derivatives strongly preclude the enzyme from decatenating or relaxing suitable substrates. Finally, we correlate their active/inactive status with docking studies of these novel compounds into the ATPase domain of hTopoIIalpha.

An efficient synthesis of embelin derivatives through domino Knoevenagel hetero Diels–Alder reactions under microwave irradiation

The synthesis of novel pyrano embelin derivatives has been achieved through domino Knoevenagel hetero Diels–Alder reactions of embelin ( 1) with paraformaldehyde and electron rich alkenes. This synthetic approach is highly efficient when microwave irradiation is used.

A new domino-Knoevenagel–hetero-Diels–Alder reaction

Various novel 3,5a,6,11b-tetrahydro-2 H,5 H-chromeno[4′,3′:4,5]thiopyrano[2,3- d][1,3]thiazol-2-ones were synthesized in 60–80% yields via domino-Knoevenagel–hetero-Diels–Alder reactions of 4-thioxo-1,3-thiazolidin-2-one with 3,7-dimethyl-6-octenal, 2-allyloxybenzaldehydes and 2-formylphenyl ( E)-3-aryl-2-propenoates with base catalysis. The possibility of stereo- and regioselective cycloaddition was investigated.