Cleavage of Diethyl Chromonyl α-Aminophosponate with Nitrogen and Carbon Nucleophiles: A Synthetic Approach and Biological Evaluations of a Series of Novel Azoles,Azines, and Azepines Containing α-Aminophosphonate and Phosphonate Groups

A convenient synthetic approach leading to a series of novel substituted azoles, azines, and azepines linked to the α-aminophosphonate moiety was achieved. The methodology depends on ring opening and ring closure (RORC) of the chromone ring of diethyl chromonyl α-aminophosphonate 1 via its reaction with nitrogen nucleophiles such as primary amines and 1,2-, 1,3-, and 1,4-bi-nucleophiles in ethanolic sodium ethoxide. Also, treatment of compound 1 with some acyclic and cyclic active methylene compounds under the same reaction conditions afforded interesting novel isolated and fused pyridine systems bearing phosphonate groups at the α-position. The screening of antimicrobial activity for the synthesized compounds indicates that connection of pyrazole, oxazepine, and benzodiazepine rings with α-aminophosphonate moiety exhibited good antimicrobial effects. Also, evaluation of their antioxidant properties shows that the compounds having 1,5-benzoxazepinyl and 1,5-benzodiazepinyl units in combination with α-aminophosphonic diester moiety are the most powerful antioxidant agents.     

Synthesis and anticancer activity of some novel diethyl {(chromonyl/pyrazolyl) [(4-oxo-2-phenyl-quinazolin-3(4H)-yl)amino]methyl}phosphonates

Abstract

The synthesis of some novel chromonyl and pyrazolyl α-aminophosphonates containing a quinazolinone ring was carried out by applying Pudovik and Kabachnik-Fields reactions under solvent- and catalyst-free conditions. The anticancer activities of these compounds were evaluated against five cancer cell lines. 3-{[(3-Phenyl/1,3-diphenyl-1H-pyrazol-4-yl)methylidene]amino}-2-phenyl-quinazolin-4(3H)-ones (3d,e) and diethyl {[3-phenyl/1,3-diphenyl-1H-pyrazol-4-yl][(4-oxo-2-phenyl-quinazolin-3(4H) yl)amino] methyl}phosphonates (4d,e) displayed the potent anticancer activities against HCT116, MCF-7 and HepG2 cell lines in comparison with the standard drug.     

Synthesis of Pyrazole‐linked Norcantharidin Analogues of Substituted Chromones

Eighteen novel pyrazole‐linked norcantharidin derivatives substituted by chromone ring were synthesized in a single step by the [3+2] 1,3‐dipolar cycloaddition reaction of norcantharidin derivatives of substituted aromatic amines with hydrazone in the presence of chloramine‐T as compared to the conventional method.     

1-Benzopyran-4(4H)-ones as novel activated alkenes in the Baylis-Hillman reaction: a simple and facile synthesis of indolizine-fused-chromones

1-Benzopyran-4(4H)-one derivatives have been successfully employed as novel activated alkenes in the Baylis-Hillman coupling with heteroaromatic-aldehydes, nitrobenzaldehydes and isatin-derivatives and the corresponding adducts, derived from pyridine-2-carboxaldehyde, have been transformed into a novel indolizine-fused-chromone framework.     

Synthesis and structure of highly substituted pyrazole ligands and their complexes with platinum(II) and palladium(II) metal ions

Reaction of 3-methoxycarbonyl-2-methyl- or 3-dimethoxyphosphoryl-2-methyl-substituted 4-oxo-4H-chromones 1 with N-methylhydrazine resulted in the formation of isomeric, highly substituted pyrazoles 4 (major products) and 5 (minor products). Intramolecular transesterification of 4 and 5 under basic conditions led, respectively, to tricyclic derivatives 7 and 8. The structures of pyrazoles 4a (dimethyl 2-methyl-4-oxo-4H-chromen-3-yl-phosphonate) and 4b (methyl 4-oxo-2-methyl-4H-chromene-3-carboxylate) were confirmed by X-ray crystallography. Pyrazoles 4a and 4b were used as ligands (L) in the formation of ML₂Cl₂ complexes with platinum(II) or palladium(II) metal ions (M). Potassium tetrachloroplatinate(II), used as the metal ion reagent, gave both trans-[Pt(4a)₂Cl₂] and cis-[Pt(4a)₂Cl₂], complexes with ligand 4a, and only cis-[Pt(4b)₂Cl₂] isomer with ligand 4b. Palladium complexes were obtained by the reaction of bis(benzonitrile)dichloropalladium(II) with the test ligands. trans-[Pd(4a)₂Cl₂] and trans-[Pd(4b)₂Cl₂] were the exclusive products of these reactions. The structures of all the complexes were confirmed by IR, ¹H NMR and FAB MS spectral analysis, elemental analysis and Kurnakov tests.     

Syntheses of 2- or 6-Substituted Chromones and Chromone Ring-opening Reaction in Polyphosphoric Acid

In an attempt to find new antitumor agents, a novel class of chromone compounds with a benzimidazoleor a benzoxazole ring in positions 2 or 6 were synthesized νia condensation in polyphosphoric acid(PPA) byusing chromone acids as the starting materials. During the preparation process, it was found that PPA couldcleave the chromone ring to produce a ring-opening compound(6). The molar ratio of the chromone com-pound (5) to the ring-opening compound (6) varied with the change of reaction temperature and time. Basedon MTT protocol, the antitumor activity of each of the compounds obtained was evaluated against three hu-man cancer cell lines: KB(oral epidermal), A2780(ovary) and Be17402 (liver). The IC50 varied from 54.7μmol/L to more than 180 μmol/L.     

A two-step,single pot procedure for the synthesis of substituted dihydropyrazolo-pyrimidines

In this study, we report a two-step, one pot tandem microwave-assisted reaction of 3-formylchromones with aminopyrazoles followed by a tin-free radical addition. A library of alkyl substituted dihydropyrazolopyrimidines was prepared using this new process.     

Convenient synthesis of linear 2H,6H-pyrano[3,2-g] chromenes from natural occurring compound; visnagin

Abstract

A simple and convenient rout for the synthesis of linear 2-imino-2H,6H-pyrano[3,2-g] chromen-6-ones and 2H,6H-pyrano[3,2-g]chromene-2,6-diones has been described starting from natural occurring furochromone; visnagin (1). Ring opening of 1 yielded 6-formyl-7-hydroxy-5-methoxy-2-methylchromone (2), which underwent reaction with different acetonitrile derivatives furnished 2-imino-2H,6H-pyrano[3,2-g] chromen-6-ones (5a–h). Acid hydrolysis of 5a–h led to the formation of 2H,6H-pyrano[3,2-g]chromene-2,6-diones (6a–h). Structures of the synthesized compounds were clarified based on their elemental analyses and spectral data. The entire target compounds were selected for in vitro anticancer activity against 60 human cancer cell lines at a single dose (10^?5 M) by the National Cancer Institute (NCI, Bethesda, USA).     

Synthesis of Chromonyl-Containing α-Aminophosphonates

A series of novel chromonyl-containing α-aminophosphonates were synthesized by a one-pot reaction from 3-formylchromones, substituted aromatic amines, and dialkylphosphites. Synthesized compounds were characterized by elemental analysis, and ¹H NMR and IR spectroscopy. Single crystal x-ray diffraction data of compound 6e was obtained, and analysis indicates that the crystal belongs to triclinic system with space group P-1, a = 9.4200(4) Å, b = 10.5970(6) Å, c = 12.3506(5) Å, α = 84.178(2)°, β = 73.5830(10)°, γ = 68.2720(10)°. V = 1098.59(9) ų, Z = 2, μ = 0.163 mm^?1, F(000) = 456, R[F²>2σ(F²)] = 0.0835, ωR(F²) = 0.2328.