Diversity-Oriented Synthesis of Spiro[chromeno[2,3-b]pyridine-3,4'-pyrazole] Derivatives via Pseudo-Three-Component Reactions.

A novel one-pot pseudo-three-component reaction of 2-amino-4H-chromen-4-ones with 4-benzylidene-5-alkyl-2-aryl-2,4-dihydro-3H-pyrazol-3-ones was investigated for the synthesis of the spiro[chromeno[2,3-b]pyridine-3,4'-pyrazole] derivatives. This procedure involved Michael addition, elimination, and hetero-Diels-Alder sequences, affording a series of spiropyrazolone-chromeno[2,3-b]pyridines in good yields that possessed cis relationships between two aryl groups and the carbonyl of the pyrazolone unit.

Annulation of 2-Aroyl D-A Cyclopropanes via Selectively Ring-Opening Process with o-Benzenediamines to Access Quinoxaline Derivatives.

An annulation reaction of 2-aroyl D-A cyclopropanes with o-benzenediamines via selective cleavage of C-C bonds of cyclopropane in the presence of DBU/Sc(OTf)3 reaction systems was developed for the direct preparation of 2-aryl-3-benzylquinoxalines. This synthetic approach tolerated a wide range of readily available aroyl-substituted D-A cyclopropanes with diverse functional groups and had operationally simple and mild reaction conditions.

Synthesis of Fully Substituted Pyrazoles with a Dicyanomethyl Group via DBU/Lewis Acid-Mediated Annulation of D-A Cyclopropanes with Arylhydrazines.

The efficient synthesis of fully substituted pyrazoles with a dicyanomethyl group was developed via an annulation reaction of 2-aroyl D-A cyclopropanes with arylhydrazines in the presence of DBU/AlCl3 reaction systems. This synthetic approach featured a wide range of readily available aroyl-substituted D-A cyclopropanes with diverse functional groups and a diversity of substituents on pyrazole products and had operationally simple and mild reaction conditions.

Synthesis of 2H-Chromeno[2,3-b]tetrahydropyridine Frameworks through Cs2CO3-Promoted Annulation of 2-Amino-4H-chromen-4-ones and 4-Benzylideneoxazol-5(4H)-ones.

This innovative reaction involved the [3+3] annulation of 2-amino-4H-chromen-4-ones and 4-benzylideneoxazol-5(4H)-ones. The process provided quick and easy access to a broad range of structurally diverse and highly functionalized 1,3,4,5-tetrahydro-2H-chromeno[2,3-b]pyridines in moderate to good yields, which possess trans-form C3 and C4 substituents.

ZnCl2-Promoted Three-Component Reaction of 2-Aminochromenones, Aromatic Aldehydes, and Quinone Monoketals: Access to 5,6-Dihydro-12H-chromeno[2,3-c]isoquinolin-12-one Derivatives.

A three-component reaction of 2-amino-4H-chromen-4-ones, aromatic aldehydes, and 4,4-dialkoxycyclohexa-2,5-dien-1-ones for the concise synthesis of chromeno[2,3-c]dihydroisoquinoline derivatives has been investigated. This reaction involved consecutive ZnCl2-promoted Micheal addition and intramolecular Friedel-Crafts alkylation. This synthetic protocol offered several advantages, including the readily accessible starting materials, good functional group tolerance, and simplicity of operation. Additionally, the structures of products obtained were determined based on X-ray diffraction studies.

Acetic Acid-Catalyzed (3 + 2) Cyclization of 2-Aroyl-3-aryl-1,1-dicyanocyclopropanes with Arylhydrazines: To trans-4-Dicyanomethyl-1,3,5-triaryl-4,5-dihydropyrazoles.

Acetic acid-catalyzed (3 + 2) cyclization reaction of substituted 2-aroyl-3-aryl-1,1-dicyanocyclopropanes with arylhydrazines was investigated for the efficient synthesis of 4-dicyanomethyl-1,3,5-triaryl-4,5-dihydropyrazoles in good yields, in which 4,5-double substituents are predominantly trans selective. This approach included the consecutive condensation, ring opening, and double nucleophilic cyclization reaction.

Acetic Acid Mediated Regioselective [3 + 3] Cycloaddition of Substituted Cyclopropane-1,1-dicarbonitriles with 1,4-Dithiane-2,5-diol.

An acetic acid mediated regioselective [3 + 3] cycloaddition of substituted cyclopropane-1,1-dicarbonitriles with in situ generated mercaptoacetaldehyde was developed for the synthesis of highly stereoselective tetrahydrothiopyranols. This transformation created two new bonds in a single operation for generating complexity in tetrahydrothiopyrans. This method is characterized by cheap and readily available starting materials, simple operation, and mild reaction conditions.

DBU-Mediated Domino Annulation Reaction of 2-Amino-4H-chromen-4-ones and Aromatic Aldehydes for Synthesis of Polysubstituted 3-Hydroxy-5H-chromeno[2,3-b]pyridinones.

A pseudo-three-component annulation reaction of substituted 2-amino-4H-chromen-4-ones with aromatic aldehydes promoted by DBU was investigated to access polysubstituted 5H-chromeno[2,3-b]pyridines. This reaction included a sequential intermolecular nucleophilic addition/Michael cyclization/intramolecular epoxidation/ring opening/aromatization sequence, which possessed excellent step and atom economy in a single operation for generating 3-hydroxy-5H-chromeno[2,3-b]pyridines from readily available substrates.

DABCO-Promoted Cyclization of 2-Amino-4H-chromen-4-ones with 2,6-Dibenzylidenecyclohexan-1-ones for the Synthesis of Chromeno[2,3-b]tetrahydroquinoline.

DABCO-promoted cyclization reaction of substituted 2-amino-4H-chromen-4-ones with substituted 2,6-dibenzylidenecyclohexan-1-ones was investigated under mild conditions. This reaction provided a novel and efficient access to the 7,8,9,10-tetrahydro-12H-chromeno[2,3-b]quinolin-12-ones in good yields, the exocyclic double bond of which is predominantly E-selective.

Yb(OTf)3-Mediated Annulation of Cyclopropane-1,1-dicarbonitriles with 2-Aminobenzaldehydes for Synthesis of Polysubstituted Quinolines.

A Yb(OTf)3-mediated annulation of cyclopropane-1,1-dicarbonitriles and 2-aminobenzaldehydes for the synthesis of polysubstituted quinolines in generally good yields was investigated. In the cascade reaction, the protocol includes ring opening, intermolecular nuclophilic addition, intramolecular nuclophilic addition, and demalononitrile aromatization, in which the malononitrile group serves as a deciduous directing group mediated by Yb(OTf)3.

Piperidine-Mediated [3 + 3] Cyclization of 2-Amino-4H-chromen-4-ones and 2-Benzylidenemalononitriles: To Access 2-Aminochromeno[2,3-b]pyridine Derivatives.

Piperidine-mediated [3 + 3] cyclization of 2-amino-4H-chromen-4-ones and substituted 2-benzylidenemalononitriles was developed for the synthesis of 2-amino-4-aryl-5H-chromeno[2,3-b]pyridin-5-one derivatives. This novel transformation provides a highly efficient and facile route to functionalized 5H-chromeno[2,3-b]pyridines from readily available substrates under mild reaction conditions.

DBU-promoted ring-opening reactions of multi-substituted donor-acceptor cyclopropanes: access to functionalized chalcones with a quaternary carbon group.

A convenient and straightforward strategy to synthesize Z-configuration chalcones with alkylcyanoacetate subunits via DBU-promoted ring-opening reactions of multi-substituted D-A cyclopropanes has been developed. This reaction did not require a transition metal catalyst and extra solvent, and haloalkanes acted as both an alkylation reagent and solvent.

DBU-Promoted Cascade Selective Nucleophilic Addition/C-C Bond Cleavage/Hetero-Diels-Alder Reactions of 2-Amino-4H-chromen-4-ones with ß-Nitrostyrenes and/or Aryl Aldehydes: Access to 5H-Chromeno[2,3-b]pyridin-5-ones.

DBU-promoted cascade selective nucleophilic addition/C-C bond cleavage/hetero-Diels-Alder reactions accompanied by aromatization of substituted 2-amino-4H-chromen-4-ones with substituted ß-nitrostyrenes or with the combined substituted ß-nitrostyrenes and aromatic aldehydes were developed for the synthesis of 2,4-diaryl-substituted 5H-chromeno[2,3-b]pyridin-5-ones. This procedure provides a highly efficient and facile route to functionalized 5H-chromeno[2,3-b]pyridines from readily available substrates under mild reaction conditions.

DBU-mediated annulation of 2-aryl-3-nitro-2H-chromenes with 1,3-cyclohexanediones for the synthesis of benzofuro[2,3-c]chromenone derivatives.

The DBU-mediated annulations of 2-aryl-3-nitro-2H-chromenes with 1,3-cyclohexanediones have been developed. This reaction involves a highly efficient domino sequence consisting of regioselective intermolecular Michael addition, intramolecular nucleophilic addition and aromatization as key unit steps. The reaction appears to be general for a variety of 2-aryl-3-nitro-2H-chromenes and tolerates the presence of aromatic moieties with electron-withdrawing and electron-donating substituents. This transformation provides a straightforward synthetic protocol for constructing benzofuro[2,3-c]chromenone derivatives.

Direct synthesis of highly functionalized furans from donor-acceptor cyclopropanes via DBU-mediated ring expansion reactions.

A DBU-mediated, unprecedented formal ring expansion reaction of 2-acyl-3-arylcyclopropane-1,1-dicarbonitriles for the synthesis of multisubstituted furan derivatives is reported. This transformation represents the regioselective ring-opening reaction of cyclopropane-1,1-dicarbonitriles and annulation using an intramolecular addition cascade reaction protocol for the synthesis of fully substituted furans includes use of readily available starting materials, mild reaction conditions, and it is transition-metal catalyst free, has good functional tolerance, and broad substrate scope.

DBU-Mediated Cyclization of Acylcyclopropanecarboxylates with Amidines: Access to Polysubstituted Pyrimidines.

DBU-mediated cyclization of 2-acyl-1-cyanocyclopropanecarboxylates with amidines for the synthesis of multisubstituted pyrimidine derivatives is described. This reaction gives a practical method for producing a diverse set of pyrimidines, having simple experimentation, readily available starting materials, a wide substrate scope, and very good yields.

Cesium-Carbonate-Mediated Benzalation of Substituted 2-Aryl-3-nitro-2 H-chromenes with Substituted 4-Benzylidene-2-phenyloxazol-5(4 H)-ones.

Cs2CO3-mediated domino benzalation reaction with a variety of 2-aryl-3-nitro-2 H-chromenes and 4-benzylidene-2-phenyloxazol-5(4 H)-ones has been realized. The reaction proceeds smoothly with a broad substrate scope, thus providing a variety of substituted ( Z)-4-(( Z)-benzylidene)chroman-3-one oximes in moderate to high yields, which were easily transformed into biologically important 4 H-chromeno[3,4- c]isoxazoles.

DBU-Promoted Cascade Annulation of Nitroarylcyclopropane-1,1-dicarbonitriles and 3-Aryl-2-cyanoacrylates: An Access to Highly Functionalized Cyclopenta[ b]furan Derivatives.

A DBU-promoted cascade annulation of nitroarylcyclopropane-1,1-dicarbonitriles and 3-aryl-2-cyanoacrylates for the synthesis of highly functionalized cyclopenta[ b]furan derivatives is described. High stereoselectivity, fused cyclopentane and furan can be established in a single reaction, highlighting the high efficiency and step-economy of this protocol. This reaction offers a novel and straightforward protocol to the synthesis of cyclopenta[ b]furans featuring the [3 + 2] cycloadditions of nitroarylcyclopropane-1,1-dicarbonitriles with 3-aryl-2-cyanoacrylates.

The Correlation of Visfatin and Its Gene Polymorphism with Non-Small Cell Lung Cancer.

Objective: To investigate the protein expression of visfatin and its gene polymorphism in non-small cell lung cancer (NSCLC) patients. Methods: The plasma level of visfatin was detected by enzyme-linked immunosorbent assay, and the genotypes rs59744560, rs9770242, and rs61330082 in the visfatin gene were detected by gene sequencing. Result: This study revealed that plasma levels of visfatin in NSCLC patients were significantly higher than the levels in healthy people (p < 0.01). The high level of plasma visfatin was found to be significantly correlated with TNM stage (p < 0.05). No mutations were detected in rs59744560 and rs9770242 loci. Three genotypes (CC, CT, and TT) were detected in rs61330082 locus, and the differences in the frequency distribution of these genotypes were significant in the two groups (p < 0.05). Central obesity and the CC genotype were independent risk factors in the pathogenesis of NSCLC (p < 0.05). Conclusion: The plasma visfatin level in NSCLC patients significantly increased, and high plasma visfatin levels were correlated with tumor stage. Gene polymorphism was found in the visfatin gene rs61330082 locus. The CC genotype might increase the risk for patients suffering from NSCLC, while the CT genotype, TT genotype, and T allele may reduce the risk of NSCLC. The rs61330082 locus can be used as genetic markers of high-risk populations.

Regioselective construction of 1,3-diaryl tetrahydroindazolones via the three-component reaction of 1,3-cyclohexanediones, ß-nitrostyrenes and arylhydrazines.

1,5,6,7-Tetrahydro-4H-indazol-4-one derivatives were successfully synthesized using a one-pot three-component system that combines substituted ß-nitrostyrenes, 1,3-cyclohexanediones and phenylhydrazines. This reaction involves a highly efficient domino sequence consisting of the aza-Michael reaction, intramolecular O-nucleophilic addition, nucleophilic addition, and ring opening of furan as the key unit steps. Notably, the highly regioselective construction of the tetrahydro-4H-indazolone moiety and the introduction of functionalized aromatic rings were achieved.